EVIDENCE OF INVOLVEMENT OF TUMOR NECROSIS FACTOR IN ADVERSE REACTIONS DURING TREATMENT OF KIDNEY ALLOGRAFT REJECTION WITH ANTITHYMOCYTE GLOBULIN

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Abstract
Serial plasma concentrations of the pyrogenic cytokines tumor necrosis factor and interleukin-1.beta. were measured during treatment of acute renal allograft rejection with antithymocyte globulin in 7 consecutive kidney transplant recipients. TNF and IL-1.beta. were measured with specific enzyme-linked immunosorbent assays. In 6 of 7 patients TNF could not be detected in the plasma before the start of the ATG infusion. During the first ATG infusion, which was accompanied by fever and other side effects in all patients, plasma TNF levels were shown to be elevated, ranging between 100 and 700 pg/ml. During the second ATG infusion, when side effects were minimal or absent, plasma TNF levels were only slightly raised. Circulating IL-1.beta. could not be detected in any of the patients before or during ATG infusion. Additional experiments showed that TNF is rapidly secreted in cultures of peripheral blood mononuclear cells incubated with both ATG and the monoclonal antibody OKT3. These findings suggest that side effects, including fever and chills, during antilymphocyte antibody infusion are related to increased plasma levels of the pyrogenic cytokine TNF.