Research ArticlesPharmacodynamic Interaction of Recombinant Human Interleukin-10 and Prednisolone Using in vitro Whole Blood Lymphocyte Proliferation
Section snippets
INTRODUCTION
Current strategy for immunosuppressive therapy involves use of combination regimens of therapeutic agents.1,2 Such combinations offer possible advantages of synergistic/additive effectiveness as well as reduction of drug-specific side effects due to reduced individual doses. Corticosteroids have been an established part of immunosuppressant drug therapy. Synergistic interactions have been observed between double drug combinations of cyclosporine, prednisolone, and sirolimus,3 justifying their
Subjects
Healthy male (n = 4) and female (n = 4, not taking birth control pills) drug-free volunteers of ages between 25 and 40 years were recruited for study. Blood was drawn at 9 AM on the day of the experiment.
Reagents
Recombinant human interleukin-10 was obtained as gift from Schering-Plough Research Institute (Kenilworth, NJ). Pred and PHA were purchased from Sigma Chemical Co. (St. Louis, MO). Serial dilutions of the drugs were made in complete media [RPMI 1640 supplemented with 2 mM L-glutamine, 20 mM HEPES,
RESULTS
Single drug sigmoidal Imax inhibition curves for IL-10 and prednisolone are presented in Figure 1. Prednisolone was more efficacious (Imax = 1.00) than IL-10, which did not completely suppress lymphocyte proliferation (Imax = 0.89 ± 0.07). However, both drugs showed appreciable inhibitory activity on lymphocyte proliferation with mean IC50 values of 16.7 and 15.7 ng/mL (IL-10) and 4.43 and 2.16 ng/mL (prednisolone) for the male and female subjects. The single-drug as well as the interaction
DISCUSSION
No significant gender-related differences were observed in the single-dose effects of IL-10 and prednisolone, although there were reports of gender-related differences for other glucocorticoids.22 The lack of significant differences, also observed by Ferron et al.,3 may be ascribed to the small study size and the time of blood collection. For female subjects, the period of blood collection was limited to within 5 days following the end of their menstrual bleeding period when gonodal steroid
Acknowledgements
This work was supported by the National Institute of General Medical Sciences, NIH, grant number GM 24211.
REFERENCES (25)
- et al.
Human interleukin-10 can directly inhibit T-cell growth
Blood
(1993) - et al.
Quantitative analysis of dose–effect relationships: The combined effects of multiple drugs or enzyme inhibitors
Adv Enzyme Regul
(1984) - et al.
Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group
Gastroenterology
(2000) - et al.
Prospects for synergistic immunosuppressive drug therapy in the coming decade
Transplant Proc
(1992) Immunopharmacologic therapy in renal transplantation
Pharmacotherapy
(1996)- et al.
Species- and gender-related differences in cyclosporine/prednisolone/sirolimus interactions in whole blood lymphocyte proliferation assays
J Pharmacol Exp Ther
(1998) - et al.
Interleukin-10: Biology, role in inflammation and autoimmunity
Ann Allergy Asthma Immunol
(1997) - et al.
IL-10 inhibits transcription of cytokine genes in human peripheral blood mononuclear cells
J Immunol
(1994) - et al.
Pharmacokinetic and adrenal interactions of interleukin-10 and prednisone in healthy volunteers
J Clin Pharmacol
(1999) - et al.
Interleukin-2-dependent autocrine proliferation in T-cell development
Nature
(1989)