Prednisone and low lymphocytes
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Correlation between bone markers and bone mineral density in postmenopausal women with osteoporosis. Endocr Pract. Effect of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res. Changes in calcium and bone metabolism during treatment with low dose prednisone in young, healthy, male volunteers.
Clin Rheumatol. Bone density at various sites for prediction of hip fractures. Prevention of early postmenopausal bone loss with cyclical etidronate therapy a double-blind, placebo-controlled study and 1-year follow-up. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. Download references. Pfizer personnel were involved in protocol development, conducting the study, data analysis and interpretation, and the decision to submit the manuscript for publication.
This study was sponsored by Pfizer Inc. Original data sources supporting the results of this manuscript can be made available on request from the corresponding author. SD participated in study conduct. All authors contributed to, read, and approved the final manuscript. SD and BGZ have no current financial interests to disclose.
The final protocol, any amendments, and informed consent documentation were reviewed and approved by the Institutional Review Board of Jasper Clinic, Inc.
All subjects provided written, informed consent to participate in the study. The study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation Good Clinical Practice guidelines.
You can also search for this author in PubMed Google Scholar. Correspondence to Arnab Mukherjee. Reprints and Permissions. Fleishaker, D. Safety and pharmacodynamic dose response of short-term prednisone in healthy adult subjects: a dose ranging, randomized, placebo-controlled, crossover study. BMC Musculoskelet Disord 17 , Download citation.
Received : 04 December Accepted : 11 June Published : 16 July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Research article Open Access Published: 16 July Safety and pharmacodynamic dose response of short-term prednisone in healthy adult subjects: a dose ranging, randomized, placebo-controlled, crossover study Dona L.
Fleishaker 1 , Arnab Mukherjee 1 , Fredrick S. Abstract Background Glucocorticoids GCs , such as prednisone, are the standard of care for several inflammatory and immunologically mediated diseases, but their chronic systemic administration is severely limited by serious adverse effects that are both dose and time dependent. Methods In this randomized, single-blind, placebo-controlled, crossover study A , 37 healthy subjects received placebo or a prednisone dose from 2.
Results Daily doses of prednisone up to 60 mg resulted in dose- and time-dependent decreases in plasma osteocalcin, plasma P1NP, serum cortisol, and absolute blood eosinophil counts. Conclusions This characterization provides important and relevant information on safety and PD responses of short-term prednisone dosing over the commonly-used clinical dose range, and also provides a reference for early clinical development of dissociated agents targeting a differentiated PD profile.
Trial registration number NCT retrospectively registered: 21 April Background Glucocorticoids GCs are commonly used to manage inflammatory and immunologically-mediated conditions [ 1 — 3 ], and continue to have a prominent place in the clinic despite having a profile of serious adverse effects that are dose- and time-dependent [ 4 , 5 ].
Study design This randomized, single-blind, placebo-controlled, crossover study A was designed to characterize the dose—response of prednisone on biomarkers of GC receptor agonism. Table 1 Treatment sequences Full size table. Results Subjects Overall, 37 subjects were screened; all were assigned to study treatment. Baseline characteristics Demographic characteristics were similar among the treatment groups. Table 2 Demographic characteristics of all treatment groups Full size table.
Full size image. Table 3 Number of subjects with abnormal and normal responses to ACTH stimulation tests performed every 2 weeks Full size table. Discussion This study was designed to characterize the dose—response and time course of prednisone effects on biomarkers of GC receptor agonism in a healthy adult population over 7 days.
Conclusions This characterization of the dose—response of prednisone on various biomarkers of GC agonism provides important and relevant information on safety and PD responses associated with short-term prednisone dosing over the commonly used clinical dose range, and provides a reference for early clinical development of dissociated agents targeting a differentiated PD profile. Google Scholar Berlin M. Funding This study was sponsored by Pfizer Inc.
Availability of data and materials Original data sources supporting the results of this manuscript can be made available on request from the corresponding author. Consent for publication Not applicable. Ethics approval and consent to participate The final protocol, any amendments, and informed consent documentation were reviewed and approved by the Institutional Review Board of Jasper Clinic, Inc. Zeiher Authors Dona L. Fleishaker View author publications.
View author publications. About this article. Cite this article Fleishaker, D. Copy to clipboard. Contact us Submission enquiries: bmcmusculoskeletaldisorders biomedcentral. I have been through a work-up in 2 medical systems Mayo and Marshfield clinic systems in Eau Claire because I changed jobs, had to change insurance and had to change doctors.
I just monitor it with a blood test every 6 months to be sure there is no major change. Ironically, in my 3 bouts with PMR, my white count goes up while on prednisone. I did read about an auto-immune leukopenia and wonder if I have it, but not diagnosed with it. Like Helpful Hug. John, Volunteer Mentor johnbishop Aug 25, Like Helpful Hug 1 Reaction. Copy link to clipboard Bookmark Report Comment. My PMR is currently in remission but I've been These effects appeared at all doses between 20 and 50 mg of prednisone.
In contrast, there was no statistically significant suppression of the total leukocyte count, total and active erythrocyte E rosette-forming lymphocytes, serum immunoglobulin concentrations, polymorphonuclear cell PMN phagocytosis, or delayed skin reactivity. This study examined, in the same individuals, prednisone's acute, dose-dependent effects on inflammation as well as biomarkers of glucose regulation and bone homeostasis.
Differential peripheral WBC counts changed significantly within hours of prednisone administration. Oral glucose tolerance tests revealed significant increases in glycaemic excursion on days 1 and 7, whereas increases in insulin and C-peptide excursions were more notable on day 7 with all doses of prednisone. The bone formation markers osteocalcin, and procollagen I N- and C-terminal peptides decreased significantly on days 1 and 7 vs placebo.
The anti-inflammatory effects of glucocorticoids GCs have proven extremely valuable in the treatment of diseases such as asthma, arthritis and transplant organ rejection.
However, the side effects following prolonged use of GCs at pharmacologic concentrations limit both their full dose-range potential and long-term use 1. Two of the most common and debilitating adverse effects of GC therapy are glucose intolerance that can lead to or exacerbate pre-existing diabetes and effects on bone that over time can develop into GC-induced osteoporosis.
GC treatment results in numerous effects influencing glucose metabolism 1 , 2 , 3. It is well known that GCs inhibit insulin secretion, induce triglyceride breakdown in adipose tissue, decrease insulin-mediated glucose uptake in skeletal muscle and increase hepatic glucose production by increasing gluconeogenesis.
Changes in glucose tolerance have been detected by oral glucose tolerance test OGTT within hours of treatment 6. However, studies examining the dose-dependent effects of GCs and, in particular, dose-dependent single dose effects have not been performed. GC therapy is also associated with accelerated decline in bone density and an increase in fractures reviewed in 7 , 8. GCs reduce osteoblast function and replication as well as increase osteoblast apoptosis 1 , 8 , 9 , Although the specific mechanism by which GCs interfere with osteoblast function remains unclear, reductions in bone formation markers have been reported to occur within days of treatment with prednisone 11 , 12 , 13 , 14 , 15 , and increases of about two- or three-fold in the relative risk of hip and vertebral fractures in patients receiving GCs have been reported 16 , Although the most severe adverse effects associated with GC treatment generally occur in patients undergoing chronic treatment with high doses, the onset of changes in glucose tolerance and bone turnover occurs soon after treatment initiation, as described above.
Given the significant therapeutic value of GCs, there has been intense effort to identify dissociated GC receptor agonists that possess the anti-inflammatory properties of classic GC receptor agonists, such as prednisolone and dexamethasone, without inducing the undesirable side effects reviewed in A better understanding of the time course relationship between GC dose and biomarkers of both efficacy and adverse effects in the same population should facilitate this search.
The current investigation, in which healthy young individuals were treated with the commonly prescribed oral GC prednisone, was conducted to identify biological markers of inflammation, glucose tolerance or bone turnover which demonstrate acute, dose-dependent relationships.
To our knowledge, this is the first published study comparing the time- and dose-dependent anti-inflammatory effects of prednisone with adverse effects in the same individuals. Principal exclusion criteria included a history of glucose intolerance, adrenal impairment and significant illnesses or abnormal laboratory evaluations.
The study was conducted in accordance with principles of Good Clinical Practice and was approved by the appropriate institutional review boards and regulatory agencies. All subjects provided written informed consent. During the course of the study, patients were required to refrain from excessive sun exposure, strenuous physical activity, use of lotion on the arms or back and use of any prescription or non-prescription medicine.
This was a randomized, double-blind, placebo-controlled, parallel group, 7-day study Study Protocol with varying doses of prednisone. The LPR to the antigen was assessed at baseline and on days 1 and 7. Allergen 0. The primary endpoint in the examination of bone turnover was serum concentration of the bone formation marker osteocalcin Bioanalytical Research Corporation, Ghent, Belgium.
All subjects treated were included in the data analyses. All analyses were performed on data collected on days 1 and 7 of dosing using the change from baseline as the outcome measure. Treatment group comparisons were evaluated using a pre-specified analysis of covariance ANCOVA model with terms for allergen stratum as well as baseline and treatment. For each outcome measure, the treatment effect each dose of prednisone compared with placebo was evaluated in a stepwise fashion, starting with the highest dose, until lack of significance was observed.
No adjustment for multiplicity was performed for multiple testing on days 1 and 7. Baseline characteristics were not significantly different among treatment groups, and are shown in Table 1. Baseline characteristics.
Data is presented as mean s. Citation: European Journal of Endocrinology , 3; Neutrophil counts increased, whereas lymphocyte and monocyte counts all decreased significantly in a dose-dependent manner.
Eosinophil counts also decreased significantly, but a dose-dependent effect was not seen at the doses of prednisone administered Supplementary Table 1S , see section on supplementary data given at the end of this article. However, this correction did not qualitatively change the results.
The values are presented as geometric mean percent change from baseline s. The increases in fasting glucose were comparable for both days 1 and 7, although the increases in fasting insulin were at least twofold higher on day 7 compared with day 1. Fasting C-peptide was also higher on day 7 compared with day 1. All prednisone doses resulted in significantly increased insulin resistance compared with placebo, using the homeostatic model assessment of insulin resistance HOMA-IR 23 , Table 3.
Furthermore, this impairment appeared to be exacerbated with longer treatment. These effects appeared to be transient since the differences compared with placebo were not seen on day 7.
Prednisone treatment decreased glucose tolerance in a dose-dependent manner as indicated by the glycaemic excursion observed during an OGTT, with corresponding increases in serum insulin Fig. Of note, the increases were numerically greater on day 7 than day 1.
Serum concentrations of the bone formation marker osteocalcin were rapidly and significantly reduced by all prednisone doses Fig.
❿Prednisone and low lymphocytes
Metrics details. Glucocorticoids GCssuch as prednisone, are the standard of care for several inflammatory and immunologically mediated diseases, but their chronic systemic administration is severely limited by serious adverse effects that are both dose and time dependent. Short-term treatment 7—14 days with oral prednisone is used for many acute inflammatory and allergic conditions.
This study was conducted to characterize the safety and pharmacodynamic PD dose—response of a 7-day course of oral prednisone on biomarkers of GC receptor agonism. In this randomized, single-blind, placebo-controlled, crossover study A37 healthy subjects received placebo or a prednisone dose from 2.
White blood cell counts and plasma samples for measuring cortisol, osteocalcin and procollagen type 1 N-propeptide P1NP were obtained at 2, 4, 8, and 12 h post-dose on Day 1, immediately prior to dosing on Days 1, 2, and 4, and at nominal dosing time on Days 0 and 8.
Urine samples for urinary N-terminal cross-linked telopeptide of type 1 collagen uNTX were collected on Days 0, 1, 2, 4, and 8. Serum samples for adiponectin were obtained prior to dosing on days 0, 1, 4 and 8.
Daily doses of prednisone up to 60 mg resulted in dose- and time-dependent decreases in plasma osteocalcin, plasma P1NP, serum cortisol, and absolute blood eosinophil counts. Absolute blood neutrophil counts increased, while blood lymphocyte counts rebounded to an increased level following an initial rapid decrease after dosing.
An increase was observed for uNTX and adiponectin. The incidence of adverse effects with prednisone was not dose related, and nervous system disorders, mainly headache, were the most frequently reported adverse effects. This characterization provides important and relevant information on safety and PD responses of short-term prednisone dosing over the commonly-used clinical dose range, and also provides a reference for early clinical development of dissociated agents targeting a differentiated PD profile.
NCT retrospectively registered: 21 April Peer Review reports. Glucocorticoids GCs are commonly used to manage inflammatory and immunologically-mediated conditions [ 1 — 3 ], and continue to have a prominent place in the clinic despite having a profile of serious adverse effects that are dose- and time-dependent [ 45 ].
Due to these known serious adverse effects, a GC such as prednisone is used at the lowest effective dose 5—7. One of the most prevalent adverse effects is that on bone remodeling, specifically, an uncoupling of bone formation and resorption in favor of bone loss via direct effects on osteoblasts [ 8 ].
Indeed, the most common form of iatrogenic osteoporosis is GC induced [ 9 ]. Many other adverse effects, such as electrolyte imbalance, weight gain, and metabolic disturbances, result from GC-induced effects on other tissues including the hypothalamic-pituitary-adrenal HPA axis [ 1011 ].
Similarly, due to a plethora of effects on leukocytes and vascular endothelial cells, such as altered cell distribution patterns, immobilization, and apoptosis, GC therapy can result in dramatic changes in circulating white blood cell profiles that may contribute to an increased risk of GC-associated infection [ 12 — 14 ].
Recent drug discovery and development efforts have focused on approaches to reduce adverse effects, while maintaining efficacy of GC therapy. These approaches include development of a modified-release prednisone formulation and discovery of selective GC receptor ligands that putatively dissociate anti-inflammatory effects mediated by genomic transrepression from adverse effects mediated by genomic transactivation [ 715 — 18 ].
Despite the present understanding of the known adverse effects of GC therapy, and recent drug development efforts to potentially dissociate efficacy and safety of GCs, the dose—response and time course of the effect of current GCs on various biomarkers of GC receptor agonism anti-inflammatory and adverse effects have not been systematically characterized. The characterization of the safety and pharmacodynamics PD of multiple doses of a standard GC such as prednisone, over the commonly used clinical dose range 2.
The present study was conducted to further characterize the safety and dose—response of 7-day prednisone administration using biomarkers of GC receptor agonism in a healthy adult population. Subjects with evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease including drug allergies, but excluding untreated, asymptomatic seasonal allergies at time of dosing or any condition possibly affecting drug absorption were excluded from the study.
This randomized, single-blind, placebo-controlled, crossover study A was designed to characterize the dose—response of prednisone on biomarkers of GC receptor agonism. Within 28 days of screening, all eligible subjects were randomly assigned to one of seven treatment sequences, each with three 7-day treatment periods separated by a day washout period Table 1. The treatments in each sequence included either three of the six prednisone doses evaluated in the study 2. In the first treatment period only, all subjects had baseline assessments on Day 0, the day prior to dosing.
Serum samples for morning cortisol were obtained immediately prior to dosing or nominal dosing time on Day 0 baseline, day prior to first dosing and on Days 1 first day of dosing2, 4, and 8, in each of the three 7-day treatment periods.
Serum samples for cortisol were obtained at 2, 4, 8, and 12 h following the first sample on Day 0 Period 1 only and following the first prednisone dose on Day 1. A radioimmunoassay Roche Diagnostics, Indianapolis, IN was used initially for measurement of cortisol in serum, but the results indicated the possibility of assay interference from prednisone and its metabolite prednisolone. Stability of cortisol was confirmed in plasma for a time period greater than the duration of storage with up to three freeze-thaw cycles.
Serum was also obtained for assaying cortisol levels on Day 8 before and 30 min after low-dose adrenocorticotropic hormone ACTH stimulation. Subjects with an abnormal low-dose ACTH stimulation response on Day 8 were administered the test again after 2 weeks. A radioimmunoassay was used for measurement of serum cortisol from the low-dose ACTH stimulation test.
Assay interference from prednisone and prednisolone was considered unlikely, since complete washout of both moieties was expected at the time these samples were obtained. Complete blood count with differential data for neutrophils, eosinophils, and lymphocytes are shown was obtained at 2, 4, 8, and 12 h post-dose on Day 1, immediately prior to dosing on Days 1, 2, and 4, and at nominal dosing time on Days 0 and 8.
Plasma samples for OC, a biomarker of bone formation, were collected serially on Day 0 at nominal dosing time and 2, 4, 8, and 12 h thereafter and serially post-dose on Day 1 2, 4, 8, and 12 himmediately prior to dosing on Days 1, 2, and 4, and at nominal dosing time on Day 8; plasma samples for procollagen type 1 N-propeptide P1NPalso a bone formation marker, were collected 12 h post-dose on Day 1, immediately prior to dosing on Days 2 and 4, and on Days 0 and 8.
Urine samples for urinary N-terminal cross-linked telopeptide of type 1 collagen uNTXa biomarker of bone resorption, were collected from the second pre-noon voiding of the bladder on Days 0, 1, 2, 4, and 8.
OC and uNTX were assayed using an enzyme-linked immunosorbent assay method. P1NP was assayed by a validated radioimmunoassay. A kinetic modification of the Jaffe reaction was used for the quantitative measurement of urinary creatinine uCr.
Pacific Biometrics, Inc. Serum samples for fasting glucose and insulin were obtained immediately prior to dosing on Days 0, 1, 2, 4, 6, and 7. For the oral glucose tolerance test OGTTthe subjects were to ingest 75 g of a glucose solution within 5 min of receiving study medication on Day 6; this solution was to be ingested within 10 min, and blood samples for glucose were then collected at 0. Serum samples for triglycerides were obtained immediately prior to dosing on Days 0, 1 and 4, and on Day 8 and, for adiponectin, immediately prior to dosing on Days 0, 1 and 4, and on Day 8.
Adverse events AEs were monitored throughout, and vital signs sitting blood pressure and pulse rate were performed at screening and prior to dosing on Days 0, 1, 4, and 8; laboratory safety tests hematology, blood chemistry, urinalysis, and hormone and chronic infection testswere performed at screening and on Day 0; a post-void weight was taken at screening and on Days 1 and 8 of each treatment period. The change from baseline in primary biomarker endpoints biomarkers of AEs and biomarkers of anti-inflammatory activity for each prednisone dose was compared with the change from baseline for placebo, using a repeated-measures crossover analysis of covariance model containing effects for sequence, period, time, dose, time by dose interaction, and subject within sequence as random effectas well as baseline as a covariate.
Overall, 37 subjects were screened; all were assigned to study treatment. Five subjects were assigned to each of the seven treatment sequences A-G and received either three active doses of prednisone 2. Ultimately, each of the treatments was received by 15 or 16 subjects. The proportion of subjects completing the study was Two subjects in treatment sequence E prednisone 20 mg, 40 mg, and placebo in Periods 1, 2, and 3, respectively and one subject in treatment sequence G prednisone 60 mg, placebo, and prednisone 5 mg in periods 1, 2, and 3, respectively discontinued from the study.
The subject in treatment sequence G discontinued during Period 2 while receiving placebo due to AEs related to the study treatment. The other two subjects discontinued from the study for reasons not related to study treatment; both subjects withdrew consent. One subject in treatment sequence E was also discontinued during Period 2 while receiving prednisone 40 mg; both subjects that discontinued during Period 2 were replaced following approval by the study statistician.
The other subject in treatment sequence E was in treatment period 1 at discontinuation, and was not replaced. Demographic characteristics were similar among the treatment groups. Subjects were aged between 18 and 50 years, and the majority were white and male Table 2. Plasma cortisol concentrations decreased rapidly following the first dose of prednisone, and then recovered in a dose-dependent manner Fig. Mean serum cortisol concentrations up to 24 h following the first daily dose of prednisone.
Pretreatment cortisol concentrations over 24 h were measured in all subjects the day prior to the first day of dosing in Period 1. Two subjects required a third test and one subject required a fourth test before their responses returned to normal.
The two subjects who did not achieve a normal response within 2 weeks received prednisone doses of either 40 mg or 60 mg in the last treatment period. Daily doses of prednisone up to 60 mg resulted in dose- and time-dependent effects on white blood cell counts.
Eosinophil counts relative to placebo demonstrated acute dose-dependent reductions on Day 1. A significant reduction versus placebo was observed as early as 2 h post-dose with prednisone 60 mg Fig.
At 4 h reductions were significant at all doses, and from 4—12 h counts relative to placebo were relatively stable Fig. Reductions in eosinophil counts relative to placebo were seen at most doses on Day 8 Fig.
Mean change from baseline difference from placebo in white blood cell counts. Eosinophil, neutrophil, and lymphocyte counts for Day 1 by hour ace and for Days 1 through 8 bdf for each daily prednisone dose. Differences in neutrophil counts relative to placebo were variable over the next 7 days: significant increases were observed with higher doses on Days 2 and 8, whereas decreases, which were significant with the lower doses, were seen on Day 4 Fig. As was observed with neutrophil counts, lymphocyte counts demonstrated acute dose-dependent reductions versus placebo on Day 1, with significant reductions observed with all doses as early as 2 h post-dose Fig.
Reductions in lymphocyte counts relative to placebo were greatest with most doses at 4 h post-dose, and were similar to placebo with the lower doses at 12 h post-dose Fig.
Daily doses of prednisone up to 60 mg resulted in dose- and time-dependent effects on biomarkers of bone metabolism. OC and P1NP are biomarkers of bone formation. On Day 1, plasma OC significantly decreased relative to placebo as early as 2 h post-dose, and continued to decrease in a dose-dependent manner until 12 h post-dose Fig.
P1NP levels increased slightly relative to placebo on Day 2, and then decreased in a dose- and time-dependent manner until Day 8 Fig. Mean change from baseline difference from placebo in biomarkers of bone metabolism. Urinary NTX is a biomarker of bone loss. The results for fasting glucose and insulin on Days 1 and 8 are shown in Table 4.
Increases from baseline in both glucose and insulin concentrations at 0. After 6 days of prednisone treatment, the changes from baseline in both glucose and insulin concentrations relative to placebo were not significant at most time points data not shown. The effect of prednisone relative to placebo on serum triglyceride levels was variable. On Day 1, prednisone 20 mg and 40 mg significantly raised triglyceride levels. On Day 8, prednisone raised triglyceride levels, but the relationship to dose was inconsistent, and the impact generally was not significant Table 4.
Dose- and time-dependent effects of prednisone on adiponectin were also observed relative to placebo. On Day 8, adiponectin was significantly increased with higher prednisone doses Table 4. However, no clear pattern for the treatment arms appeared in either assessment. There were no serious adverse events SAEs or deaths reported. There were no clinically significant changes in vital signs or body weight at any time point.
The incidence of AEs with prednisone was not dose related. Three subjects reported severe AEs; all were headaches experienced while on prednisone 2. This study was designed to characterize the dose—response and time course of prednisone effects on biomarkers of GC receptor agonism in a healthy adult population over 7 days.
Daily doses of prednisone up to 60 mg were generally well-tolerated and resulted in dose- and time-dependent effects on a number of biomarkers. As would be expected, a decrease relative to placebo was noted in biomarkers of bone formation OC and P1NPwhereas there was an increase in a biomarker of bone turnover uNTX.
❾-50%}Prednisone and low lymphocytes. Human lymphocyte subpopulations. Effect of corticosteroids
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I just turned 60, I have had PMR for 20 months now, on prednisone since last May and I just got recent blood tests back and my absolute lymphocytes are below. I've read that steroids and PMR can both cause a reduction in lymphocytes. This condition puts you at a higher risk for cancers and bacterial and viral infections. My question is: have others experienced a low absolute lymphocyte condition and is there anything that can be done to improve the levels?
Interested in more discussions like this? Hello greggWelcome to Mayo Clinic Connect. My PMR is currently in remission but I've been on prednisone twice and was aware of a lot of different side effects but was not aware that it can cause a reduction in white blood cells lymphocytes. I do know that in general prednisone can lower your immunity and thus make it easier for infections, etc.
There is another discussion you may be interested in reading through and meeting other members with PMR while we wait to see if other members have suggestions for you.
PMR Anyone? I did find some information that speaks to having low white blood cell count — Excerpt from following article — "While no specific foods or diet changes are proven to increase production of white blood cells, if you have low WBC leukopeniait is very important to practice good hygiene, hand-washing, and food safety practices.
Neutrophils are the cells that fight bacterial infection. Has your doctor or rheumatologist provided any suggestions to help with the low lymphocytes number? Jump to this post. I too have lower wbc and reduced leukocytes since on prednisone.
Even at low dose of 2mg day for 10 months. Also some digestive issues similar to posting re: diverticulitis, diarrhea more than constipation.
Thank you Kathy for sharing your experience. I have had a low white blood count for about 16 years. It was found on a random blood test.
I have been through a work-up in 2 medical systems Mayo and Marshfield clinic systems in Eau Claire because I changed jobs, had to change insurance and had to change doctors.
I just monitor it with a blood test every 6 months to be sure there is no major change. Ironically, in my 3 bouts with PMR, my white count goes up while on prednisone. I did read about an auto-immune leukopenia and wonder if I have it, but not diagnosed with it. Like Helpful Hug.
John, Volunteer Mentor johnbishop Aug 25, Like Helpful Hug 1 Reaction. Copy link to clipboard Bookmark Report Comment. My PMR is currently in remission but I've been John, Volunteer Mentor johnbishop Oct 4, In reply to johnbishop " gregg and kathylovgren - I was hoping more members with low white blood count would be Mine have been low too. I just found out so I have not discussed it with my doctor. Please sign in or register to post a reply. Join Already have an account?
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In all cases the absolute numbers of T cells and of B cells were decreased by prednisone. The density gradient distribution of the lymphocytes did not. Prednisone caused marked lymphopenia, suppression of phytohemagglutin (PHA) lymphocyte transformation and PMN adherence 4 hr after ingestion. Conclusions The early drop in ALC with persistent lymphopenia as well as the and decreased clearance have been seen with high-dose corticosteroids in. Neutrophil counts increased, whereas lymphocyte and monocyte counts all decreased significantly in a dose-dependent manner. Eosinophil counts also decreased. My PMR is currently in remission but I've been on prednisone twice and was aware of a lot of different side effects but was not aware that it. Effects of low-dose prednisone on bone metabolism.Use of glucocorticoids for anti-inflammatory efficacy is limited by their side effects. This study examined, in the same individuals, prednisone's acute, dose-dependent effects on inflammation as well as biomarkers of glucose regulation and bone homeostasis.
Differential peripheral WBC counts changed significantly within hours of prednisone administration. Oral glucose tolerance tests revealed significant increases in glycaemic excursion on days 1 and 7, whereas increases in insulin and C-peptide excursions were more notable on day 7 with all doses of prednisone. The bone formation markers osteocalcin, and procollagen I N- and C-terminal peptides decreased significantly on days 1 and 7 vs placebo.
The anti-inflammatory effects of glucocorticoids GCs have proven extremely valuable in the treatment of diseases such as asthma, arthritis and transplant organ rejection. However, the side effects following prolonged use of GCs at pharmacologic concentrations limit both their full dose-range potential and long-term use 1.
Two of the most common and debilitating adverse effects of GC therapy are glucose intolerance that can lead to or exacerbate pre-existing diabetes and effects on bone that over time can develop into GC-induced osteoporosis. GC treatment results in numerous effects influencing glucose metabolism 1 , 2 , 3.
It is well known that GCs inhibit insulin secretion, induce triglyceride breakdown in adipose tissue, decrease insulin-mediated glucose uptake in skeletal muscle and increase hepatic glucose production by increasing gluconeogenesis. Changes in glucose tolerance have been detected by oral glucose tolerance test OGTT within hours of treatment 6.
However, studies examining the dose-dependent effects of GCs and, in particular, dose-dependent single dose effects have not been performed. GC therapy is also associated with accelerated decline in bone density and an increase in fractures reviewed in 7 , 8.
GCs reduce osteoblast function and replication as well as increase osteoblast apoptosis 1 , 8 , 9 , Although the specific mechanism by which GCs interfere with osteoblast function remains unclear, reductions in bone formation markers have been reported to occur within days of treatment with prednisone 11 , 12 , 13 , 14 , 15 , and increases of about two- or three-fold in the relative risk of hip and vertebral fractures in patients receiving GCs have been reported 16 , Although the most severe adverse effects associated with GC treatment generally occur in patients undergoing chronic treatment with high doses, the onset of changes in glucose tolerance and bone turnover occurs soon after treatment initiation, as described above.
Given the significant therapeutic value of GCs, there has been intense effort to identify dissociated GC receptor agonists that possess the anti-inflammatory properties of classic GC receptor agonists, such as prednisolone and dexamethasone, without inducing the undesirable side effects reviewed in A better understanding of the time course relationship between GC dose and biomarkers of both efficacy and adverse effects in the same population should facilitate this search.
The current investigation, in which healthy young individuals were treated with the commonly prescribed oral GC prednisone, was conducted to identify biological markers of inflammation, glucose tolerance or bone turnover which demonstrate acute, dose-dependent relationships.
To our knowledge, this is the first published study comparing the time- and dose-dependent anti-inflammatory effects of prednisone with adverse effects in the same individuals. Principal exclusion criteria included a history of glucose intolerance, adrenal impairment and significant illnesses or abnormal laboratory evaluations.
The study was conducted in accordance with principles of Good Clinical Practice and was approved by the appropriate institutional review boards and regulatory agencies. All subjects provided written informed consent. During the course of the study, patients were required to refrain from excessive sun exposure, strenuous physical activity, use of lotion on the arms or back and use of any prescription or non-prescription medicine.
This was a randomized, double-blind, placebo-controlled, parallel group, 7-day study Study Protocol with varying doses of prednisone. The LPR to the antigen was assessed at baseline and on days 1 and 7. Allergen 0. The primary endpoint in the examination of bone turnover was serum concentration of the bone formation marker osteocalcin Bioanalytical Research Corporation, Ghent, Belgium.
All subjects treated were included in the data analyses. All analyses were performed on data collected on days 1 and 7 of dosing using the change from baseline as the outcome measure. Treatment group comparisons were evaluated using a pre-specified analysis of covariance ANCOVA model with terms for allergen stratum as well as baseline and treatment. For each outcome measure, the treatment effect each dose of prednisone compared with placebo was evaluated in a stepwise fashion, starting with the highest dose, until lack of significance was observed.
No adjustment for multiplicity was performed for multiple testing on days 1 and 7. Baseline characteristics were not significantly different among treatment groups, and are shown in Table 1.
Baseline characteristics. Data is presented as mean s. Citation: European Journal of Endocrinology , 3; Neutrophil counts increased, whereas lymphocyte and monocyte counts all decreased significantly in a dose-dependent manner.
Eosinophil counts also decreased significantly, but a dose-dependent effect was not seen at the doses of prednisone administered Supplementary Table 1S , see section on supplementary data given at the end of this article.
However, this correction did not qualitatively change the results. The values are presented as geometric mean percent change from baseline s. The increases in fasting glucose were comparable for both days 1 and 7, although the increases in fasting insulin were at least twofold higher on day 7 compared with day 1.
Fasting C-peptide was also higher on day 7 compared with day 1. All prednisone doses resulted in significantly increased insulin resistance compared with placebo, using the homeostatic model assessment of insulin resistance HOMA-IR 23 , Table 3.
Furthermore, this impairment appeared to be exacerbated with longer treatment. These effects appeared to be transient since the differences compared with placebo were not seen on day 7. Prednisone treatment decreased glucose tolerance in a dose-dependent manner as indicated by the glycaemic excursion observed during an OGTT, with corresponding increases in serum insulin Fig.
Of note, the increases were numerically greater on day 7 than day 1. Serum concentrations of the bone formation marker osteocalcin were rapidly and significantly reduced by all prednisone doses Fig.
Significant increases in a marker of bone resorption, serum NTX, also occurred for the higher prednisone doses. There was no discernible effect of prednisone on either day 1 or 7 data not shown. The aim of the present study was to evaluate several dose-responsive, anti-inflammatory efficacy biomarkers and to compare the time-course of these dose-dependent, anti-inflammatory changes with those observed for indicators of glucose tolerance and bone metabolism following short-term administration of the widely used GC, prednisone.
Prednisone doses were selected to be representative of the therapeutic dose range typically used in clinical practice. Supraphysiologic GC activity has long been established to suppress the hypothalamic—pituitary—adrenal HPA axis. As anticipated, all prednisone doses suppressed serum ACTH compared with placebo acutely.
To our knowledge, these acute dose-dependent differences between supraphysiologic prednisone doses on the HPA axis suppression have not been previously described.
In addition, acute, dose-dependent changes in peripheral WBC count were observed following single and multiple doses of all prednisone doses studied, as shown previously 24 , 25 , However, it was unknown whether attenuation of the LPR was either dose-responsive or a sensitive biomarker of GC anti-inflammatory effects. The inability to demonstrate any significant effects on LPR size with lower prednisone doses suggests that the LPR may not be adequately sensitive to assess less potent anti-inflammatory effects.
A notable complication was the significant inter-subject variability observed in LPR response, which may have served to obscure detection of the effect, particularly for the lower prednisone doses. A post hoc analysis of the LPR data revealed several parameters which could be optimized to reduce the observed variability.
Supraphysiologic GC activity leads to impaired glucose tolerance 1 , 2 , 3. It was recently demonstrated that low doses of prednisolone 7. GC-induced insulin resistance certainly contributed to the glucose intolerance and was evident in the elevated fasting insulin and C-peptide concentrations noted on day 7 compared with day 1, and consistent with the HOMA-IR findings. It should be noted that although all enrolled subjects demonstrated normal glucose tolerance at baseline, they were required to demonstrate hypersensitivity to allergen and had received a cutaneous allergen challenge prior to glucose administration for the OGTT.
It is unknown what contribution this hypersensitive state may have had in exacerbating or predisposing to glucose intolerance following even a single prednisone dose. Furthermore, it has been reported that interstitial hyperglycaemia associated with prednisolone treatment is predominantly manifested in the afternoon and evening in patients receiving prednisolone treatment while undergoing continuous glucose monitoring Accordingly, the OGTT was conducted during the mid-late afternoon.
Nonetheless, these results suggest that in susceptible individuals, modest doses of prednisone may impair glucose tolerance acutely. It remains unknown whether the acute impairment of glucose tolerance i. It is interesting to note that the glycaemic excursion during the OGTT after multiple prednisone doses appeared to diminish over time.
Of the bone formation markers analysed, osteocalcin was the most sensitive to GC treatment. Although GCs have been reported to affect primarily bone formation, a significant increase in bone resorption, as indicated by increased serum NTX, was observed for higher prednisone doses. Finally, Dkk-1 has previously been suggested to play a role in GC-induced osteoporosis by interfering with canonical Wnt signaling. In contrast to results from in vitro studies with cultured human osteoblasts 33 , 34 , however, in this study, Dkk-1 concentrations were found to be unchanged in response to prednisone administration.
Possible explanations for these results are that longer prednisone administration may be required to affect Dkk-1 expression or that the GC-induced effects on Dkk-1 occur locally and are not detectable in serum. In summary, dose-responsive anti-inflammatory efficacy biomarkers were identified following single and multiple prednisone dose administration. The short time-course of these dose-dependent, anti-inflammatory changes was also observed for markers of glucose tolerance and bone metabolism.
To our knowledge, this is the first time a comprehensive review of GC effects on inflammation, glucose, and bone has been conducted in the same healthy individuals. S Mesens and S Ramael have no conflict of interests to report. The authors want to thank Gary Herman and Alice Reicin for their contributions to the study design and for several helpful discussions, as well as Belma Dogdas for her analysis of the cutaneous allergen challenge results.
Dr Brian Schapiro performed the quantitative histological analysis of skin biopsy samples. We are also very grateful to Dr Paul Atkins for his insights, suggestions and critical reviews of drafts of this manuscript. Mechanisms involved in the side effects of glucocorticoids.
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Diabetes Care 25 — Glucocorticoid-induced diabetes mellitus: prevalence and risk factors in primary renal diseases. Clinical Practice c54 — c Schneiter P , Tappy L. Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans.
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