title: Pharmacoimmunodynamic interactions of interleukin-10 and prednisone in healthy volunteers.
abstract: OBJECTIVE
  The pharmacoimmunodynamic interactions of recombinant human interleukin-10 and prednisolone were examined in 12 normal male volunteers.
  
  
  METHODS
  Single doses of interleukin-10 (8 microg/kg subcutaneous injection), interleukin-10 with prednisone (15 mg by mouth), placebo with prednisone, or placebo were administered. Drug concentrations yielded pharmacokinetic parameters. Response measurements included whole blood lipopolysaccharide-stimulated cytokine (tumor necrosis factor-alpha, interleukin-1beta) production, phytohemagglutinin-stimulated whole blood lymphocyte proliferation, and differential white blood cell counts (including monocytes, lymphocytes, and neutrophils). Extended indirect-response models were used to deal with diverse drug interactions in assessing single and joint effects of interleukin-10 and prednisolone.
  
  
  RESULTS
  No pharmacokinetic alterations in interleukin-10 or prednisolone were found. Dosing with interleukin-10 produced strong inhibition of ex vivo cytokine production for the 24-hour postdosing period, whereas prednisolone, the active form of prednisone, was partly inhibitory for only 3 hours. Prednisolone significantly inhibited (P < .05) ex vivo lymphocyte proliferation for 6 hours, whereas interleukin-10 failed to alter this measure. Their joint effects on these responses were inhibitory consonant with the stronger agent. Marked changes in various leukocyte kinetics occurred. The steroid caused monocytopenia, lymphocytopenia, and neutrophilia, with IC50 or SC50 values of 10 to 20 ng/mL. Interleukin-10 elevated monocytes and neutrophils and lowered lymphocyte counts, with IC50 or SC50 values of 0.7 to 1.3 ng/mL. Dynamic modeling showed loss of prednisolone effects on monocytes and additive steroid/interleukin-10 effects on lymphocytes and neutrophils, with neutrophils exhibiting greater changes in net response.
  
  
  CONCLUSIONS
  Interleukin-10 and prednisolone interacted favorably for the measured pharmacoimmunodynamic indices with no kinetic alterations but net responses that were similar to or greater than effects produced by the more strongly acting agent.
authors: Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, USA.
authors: A
authors: A
authors: Chakraborty
authors: R A
authors: RA
authors: Blum
authors: D L
authors: DL
authors: Cutler
authors: W J
authors: WJ
authors: Jusko
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology*; D019540:Area Under Curve; D002455:Cell Division; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008432:Mathematical Computing; D008962:Models, Theoretical; D011241:Prednisone / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D011241:Prednisone