INTERLEUKIN-1 BINDING TO ITS TYPE-I, BUT NOT TYPE-II RECEPTOR, MODULATES THE IN-VIVO ACUTE-PHASE RESPONSE

Neutralizing monoclonal antibodies against the murine interleukin 1 (IL-1) type I (mAb 35F5) and type II receptor (mAb 4E2) were used to passively immunize mice prior to exogenous murine IL-alpha administration or a sterile-turpentine induced abscess. When mice were passively immunized with 35F5, the anorexia, weight loss and increased plasma acute phase protein levels in response to exogenous IL-1 alpha administration or a turpentine abscess were significantly attenuated. In contrast, passive immunization,vith 4E2 had only variable effects on food intake, body weight and the hepatic acute phase response in mice administered IL-1 alpha. In mice following a turpentine abscess, type II receptor blockade (4E2) either had no effect, or in some cases, actually increased the plasma IL-6 and acute phase protein responses. We conclude that in response to a turpentine abscess, the anorexia, weight loss and the induction of several hepatic acute phase reactants result in part from IL-1 binding to its type I receptor, Binding of IL-1 to the type II IL-1 receptor does not appear to be involved in the induction of these host nonspecific responses to inflammation. (C) 1995 Academic Press Limited.