Toxicity of OKT 3 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 treated with a conventional dose of OKT3 (5 mg daily) for acute rejection. We also investigated cytokine release and activation of complement and neutrophils as all of these are held responsible for OKT3-induced side 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 OKT3, TNF peak levels were significantly lower than after a conventional dose of OKT3. In contrast to our data on conventional dose OKT3 treatment, the first administration of low-dose OKT3 did not induce complement activation as reflected by C3a and C4b/c levels in plasma. Finally, the increase in neutrophil degranulation products lactoferrin and elastase-₁- was much less following 0.5 mg OKT3 than following 5 mg. We conclude that OKT3-induced toxicity is dose-dependent and is mediated not only by cytokine release but also by activation of complement and neutrophils.