摘要：

Interleukin 1 (IL-1) plays an important role in defense mechanisms by increasing body temperature, inducing the synthesis of a variety of lymphokines and hepatic acute phase proteins and acting as a chemoattractant for lymphocytes. However, in some microenvironments such as injured tissue or joint spaces, elevated IL-1 levels may contribute to pathologic processes, for example, proliferation and fibrosis of tissue involved in formation as well as degradation of matrix and abnormal tissue architecture. To investigate potential mechanisms that may lead to excessive production of IL-1, we have examined the ability of IL-1 to participate in an amplification event by inducing its own gene expression leading to synthesis of biologically active IL-1. When injected into , recombinant induced biphasic , and during the second temperature elevation 3 hr later, a circulating pyrogenic material was detected by passive transfer of plasma to other . Induction of the biphasic was not caused by endotoxin contamination of the recombinant IL-1. The 3-hr circulating pyrogen was heat-labile and was not residual injected . Chromatographic separation of this plasma and biologic assay suggested that it was new IL-1 of origin. We next incubated blood mononuclear cells with recombinant and measured the and levels of IL-1 by bioassay using the .G4.1 T cell line. In order to control for the carryover of recombinant used to stimulate the mononuclear cells (MNC), we used neutralizing antibodies that were specific for or . The results of these neutralizations showed that recombinant induces the synthesis of in MNC in vitro. These results were verified with a radioimmunoassay specific for . At concentrations of 100 ng/ml, induced production in the MNC culture, and this was associated with decreased production of immunoreactive . Adding to the cultures prevented the decreased production of induced by high concentrations of . Using nonadherent MNC, we observed an increase in as well as after 4 hr of exposure to recombinant . These results demonstrate that induces biologically active and immunoreactive from MNC in vitro and that the same concentrations of induce gene expression for both forms of IL-1.(ABSTRACT TRUNCATED AT 400 WORDS).

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