Production of interleukin I during the course of inflammation and its biological significance.

In order to shed some light on the mechanism by which inflammation modulates the immune response, the kinetics of IL-1 production and of the cells producing it as well as the control mechanisms involved were studied in a variety of animal models. In the case of casein-induced peritoneal inflammation in rabbits, IL-1 beta mRNA expression was found to be limited to the early stage--peaking at 2 h and lasting for only 5 h, a period corresponding to that in which new antigen introduction induces an enhanced immune response. This suggests that IL-1 beta is an inflammation-induced immune potentiation factor. Among 5-h peritoneal exudate cells (PEC) staining with anti-rabbit-IL-1 beta goat antibody, 99% were PMNs. Surprisingly, 9-h and 16-h PECs, which display negative IL-1 activity, also stained for IL-1 beta antigen. This seemingly contradictory data can be explained by the existence of a hypothetical processing protease subject to limited activation, and by a newly isolated 13 kD IL-1 antagonist produced during the later stages of inflammation.