Interleukin 1 (IL-1) is a major immunoregulatory molecule in mammals, and it has a critical role in defense mechanisms against a variety of environmental insults. "Tumor necrosis factor" (TNF) is another macrophage-derived cytokine whose activities are very similar to those of IL-1. The great importance of these proteins in self defense suggests that they may have been conserved through evolution. Results from this laboratory suggest that IL-1 is found in the echinoderms and protochordates. The major goals of the proposed research are to define the amino acid sequence and corresponding DNA sequence for invertebrate IL-1, to trace the emergence of the cells responsible for its production and release, and to characterize the functions of this mediators in the invertebrates. The invertebrate homolog of TNF will also be sought and studied in parallel with IL-1. The discovery of a homolog of the immunoregulatory molecule, IL- 1, in the starfish strongly suggests that chemical signaling molecules are important in defense mechanisms of organisms at all levels of complexity. This research will provide new information on the mechanisms of self defense in invertebrates. In addition to its intrinsic interest, however, information on the function of this immunoregulatory molecule in invertebrates may provide new insights into the mechanism of its multiple actions in higher animals.