A PILOT TRIAL OF RECOMBINANT HUMAN INTERLEUKIN-10 IN KIDNEY TRANSPLANT RECIPIENTS RECEIVING OKT3 INDUCTION THERAPY1,2

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Abstract
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. Patients received 0.1 (n=6), 1 (n=6), or 10 μg/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. 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-α (TNF-α) 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 μg/kg rhIL-10, respectively. Values for 24-hr TNF-α 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 μg/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-γ in rhIL-10-pretreated patients. Although none of the patients who received placebo or 0.1 or 1 μg/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. Pretreatment with doses of up to 1 μg/kg rhIL-10 is safe and reduces the release of TNF-α induced by OKT3. However, higher doses might promote early sensitization to OKT3.