Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation.
Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole-blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC(50) of 3.3 ng/mL and I(max) value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC(50) and 0.89 for I(max). There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent.
Chakraborty
Abhijit
A
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.
Jusko
William J
WJ
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D010835:Phytohemagglutinins; D011239:Prednisolone / Q000097:blood / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016753:Interleukin-10; D011239:Prednisolone