PENTOXIFYLLINE DOES NOT PREVENT THE CYTOKINE-INDUCED FIRST DOSE REACTION FOLLOWING OKT3 - A RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

The use of OKT3 as an immunosuppressive agent is accompanied by increa sed cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS), Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with met hylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior t o beginning OKT3 as therapy for acute rejection. Patients were observe d, and symptoms scored semiquantitatively. Despite the presence of the rapeutic PTF levels (721+/-726 ng/ml), the frequency and severity of s ide effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups, Plasma l evels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted f ollowing OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretrea tment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.