ADMINISTRATION OF OKT3 AS A 2-HOUR INFUSION ATTENUATES FIRST-DOSE SIDE-EFFECTS

Background. Use of the murine CD3 monoclonal antibody OKT3 is limited by first-dose side effects, which are thought to be caused by the rele ase of inflammatory mediators. Because these processes might be influe nced by the speed of administration, we compared a 2-hr OKT3 infusion with the bolus infusion usually applied nowadays. Methods. Eighteen re nal allograft recipients were prophylactically treated with OKT3 and r andomized to receive the first dose either as a 2-hr infusion or as an intravenous bolus infusion. Clinical side effects score and the occur rence of complement activation, cytokine release, and activation of ne utrophils were determined. Results. Two-hour infusion of OKT3 complete ly prevented the occurrence of dyspnea, reduced the incidence of other side effects, and attenuated complement activation. Cytokine release and depletion of peripheral blood lymphocytes were similar in both gro ups. Conclusions. Thus, complement activation seems to play an additio nal role in the development of side effects after the first OKT3 dose.