A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy
Faculty of Medicine and Health Sciences
Transplantation. - Baltimore, Md, 1963, currens
, p. 999-1006
Background. We conducted a randomized, double-blind, placebo-controlled, rising single-dose study to investigate the effects of recombinant human (rh) interleukin (IL) 10 in renal transplant patients who received OKT3 as induction therapy, Methods, Patients received 0.1 (n = 6), 1 (n = 6), or 10 mu g/kg (n = 3) rhIL-10 or placebo (n = 6) intravenously 30 min before the first injection of 5 mg of OKT3, We monitored IL-10 serum levels, the effect of rhIL-10 on OKT3-induced cytokine production, clinical toxicity, and the incidence of immunization against OKT3, Results, Serum IL-10 levels in the three experimental groups reached 0.8 +/- 0.2, 7.9 +/- 1.3, and 118.6 +/- 7.3 ng/ml (mean +/- SEM), respectively, 30 min after rhIL-10 injection, Peak plasma levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 2953 +/- 1599 pg/ml in patients injected with OKT3 and placebo to 447 +/- 155, 703 +/- 246, and 459 +/- 246 pg/ml in patients injected with 0.1, 1, and 10 mu g/kg rhIL-10, respectively, Values for 24-hr TNF-alpha area under the curve decreased from 8988 +/- 3551 pg.hr/ml in control patients to 2284 +/- 494, 3950 +/- 955, and 2420 +/- 931 pg.hr/ml for the 0.1, 1, and 10 mu g/kg rhIL-10 dose groups, respectively (P = 0.045), There was also a trend toward reduced plasma levels of IL-2, IL-8, and interferon-gamma in rhIL-10-pretreated patients, Although none of the patients who received placebo or 0.1 or 1 mu g/kg rhIL-10 developed an IgM antibody response directed against OKT3 during the first 10 days, this occurred in all three patients who received the highest rhIL-10 dose, In two of these patients, neutralization of OKT3 was associated with a reversible acute rejection episode, Conclusions, Pretreatment with doses of up to 1 mu g/kg rhIL-10 is safe and reduces the release of TNF-alpha induced by OKT3, However, higher doses might promote early sensitization to OKT3.