Use of indomethacin to minimize the adverse reactions associated with orthoclone OKT3 treatment of kidney allograft rejection

In solid organ transplant recipients, serious adverse reactions have been associated with the initial doses of Orthoclone OKT3. Most patients receiving OKT3 report a "flu-like" syndrome, characterized by fever, chills, nausea, vomiting, and headache. There is evidence from both in vitro and in vivo studies of an association between cytokine release and the systemic reactions noted during the initial 24-48 hr of OKT3 therapy. Inhibition of cytokine release by the use of cyclooxygenase inhibitors has been reported to modify the symptom complex exhibited in both animals and humans. These results prompted the design of a randomized, placebo-controlled, multicenter study to evaluate the effects of the cyclooxygenase inhibitor, indomethacin, during the first 48 hr of OKT3 therapy on the incidence and severity of first-dose reactions and the expression of cytokines in patients undergoing acute renal allograft rejection.