TOXICITY OF OKT3 INCREASES WITH DOSAGE - A CONTROLLED-STUDY IN RENAL-TRANSPLANT RECIPIENTS

In the present study we prospectively compared side effects occurring in 12 patients after the first administration of low-dose OKT3 (0.5 mg twice daily) induction therapy with those in 10 patients who were tre ated with a conventional dose of OKT3 (5 mg daily) for acute rejection . We also investigated cytokine release and activation of complement a nd neutrophils as all of these are held responsible for OKT3-induced s ide effects. Low-dose OKT3 resulted in a significantly decreased side effects score compared to that after a conventional dose of OKT3 (1.8 vs 5.1, p = 0.0006). Following the first administration of low-dose OK T3, TNF peak levels were significantly lower than after a conventional dose of OKT3. In contrast to our data on conventional dose OKT3 treat ment, the first administration of low-dose OKT3 did not induce complem ent activation as reflected by C3a and C4b/c levels in plasma. Finally , the increase in neutrophil degranulation products lactoferrin and el astase-proportional to(1)-antitrypsin was much less following 0.5 mg O KT3 than following 5 mg. We conclude that OKT3-induced toxicity is dos e-dependent and is mediated not only by cytokine release but also by a ctivation of complement and neutrophils.