OKT3-INDUCED NEPHROTOXICITY IS ASSOCIATED WITH RELEASE OF GROUP-II SECRETORY PHOSPHOLIPASE A(2)

Administration of the murine IgG2a CD3 monoclonal antibody OKT3 exerts a transient nephrotoxic effect. Increased levels of group II secretor y phospholipase A(2) (sPLA(2)-II) might account for this nephrotoxicit y as sPLA(2)-II induces the biosynthesis of prostaglandins, vasoactive lipid mediators that influence glomerular haemodynamics and renal fun ction. Furthermore. extracellular phospholipases seem to be involved i n proximal tubular cell injury. We studied plasma sPLA(2)-II levels in relation to circulating creatinine, tumour necrosis factor alpha, int erleukin 6 and C-reactive protein levels in 15 renal allograft recipie nts receiving rejection treatment with OKT3. As a control group, we st udied 15 renal allograft recipients receiving rejection treatment with methylprednisolone. A maximal fourfold increase in sPLA(2)-II levels was observed 48 h after the first OKT3 administration, preceded by inc reased tumour necrosis factor a and interleukin 6 levels and accompani ed by increased C-reactive protein levels. Creatinine levels reached a maximal increase 72 h after initiation of treatment. During methylpre dnisolone treatment no increase in any of the studied parameters was o bserved. Thus, administration of OKT3 induces increased sPLA(2)-II lev els. presumably via generation of cytokines. we hypothesize that sPLA( 2)-II may contribute to the nephrotoxic effect of OKT3 by inducing vas oconstrictive prostaglandins and renal tubular cell injury.