Effects of human interleukin-1 on natural killer cell activity: is fever a host defense mechanism for tumor killing?

Interleukin-1 (IL-1) represents a family of polypeptides with a wide range of biological activities. cDNA from two gene products has been cloned; there are probably more. The human IL-1 family plays an important role in the pathogenesis of many diseases and functions as a key mediator of host response to various infectious, inflammatory, neoplastic, and immunologic challenges. Recombinant mouse (pI 5) and recombinant human (pI 7) IL-1s are being used to confirm the multiple biological properties of IL-1s. Some IL-1 biological activities seem to be involved with mechanisms of host tumor killing. Incubating purified or recombinant human IL-1 with human peripheral blood mononuclear cells in the presence of IL-2 or interferon-alpha results in a synergistic enhancement of certain tumor cells. More recent results indicate that IL-1 exhibits direct cytotoxicity for tumor cells in vitro. The peripheral blood mononuclear cells of patients with tumors demonstrate decreased production of IL-1 when challenged with endotoxin and show a comparable decrease in natural killer activity; adding exogenous IL-1 reverses this defect in these patients. However, induction of hepatic acute-phase proteins such as serum amyloid A serves as a negative feedback since the amyloid protein suppresses natural killer activity. Moreover, natural killer cell activity in the presence of IL-1 or interferon-alpha is suppressed by incubating temperatures of 39 degrees C. This effect is not reversed by inhibitors of prostaglandin synthesis. IL-1 is clearly important to host defense against malignancy, but some aspects of IL-1 biology seem to exert a contrary influence.