INCREASE OF STNF RECEPTOR LEVELS IN ACUTE RENAL-ALLOGRAFT REJECTION AFTER TREATMENT WITH OKT3

The use of OKT3 is associated with severe clinical side-effects, Adver se reactions are partly attributed to release of tumour necrosis facto r (TNF). TNF binds to two receptors on the outer membranes of most hum an cell lines. Shedding of these proteins (sTNFR-p55 and sTNFR-p75) ma y block biological effects of TNF. Here we show a fair correlation bet ween serum levels of sTNFRs and renal function as measured by glomerul ar filtration rate (GFR). In addition we assessed levels of sTNFR-p55 and sTNFR-p75, corrected for reduced renal clearance, in renal allogra ft rejection and following treatment with OKT3. Corrected serum levels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12 renal allograf t patients treated for an acute rejection episode with either OKT3 or methylprednisolone (MPNS). Serum levels of CSLsTNFR-p55 and CSLsTNFR-p 75 in both groups prior to anti-rejection treatment were not elevated. CSLsTNFRs peaked at 1 h after the administration of OKT3, whereas in the MPNS group CSLsTNFRs remained unchanged. We conclude that in acute renal transplant rejection CSLsTNFRs increase after treatment with OK T3. In spite of high circulating sTNFRs levels all OKT3-treated patien ts suffered from clinical side-effects.