9304309 Habicht The cytokines interleukin 1 (IL-1), tumor necrosis factor (TNF), and interleukin 6 (IL-6) are major immunoregulatory molecules, produced by macrophages, that act as molecular orchestrators of host defense mechanisms against a variety of environmental insults. The immunological effects of these cytokines are many. Equally important are their effects as mediators of nonspecific host defense mechanisms. The exquisite action of cytokines in fine tuning and controlling the inflammatory/immune response led to the hypothesis that these molecules have been highly conserved through evolution. It was reasoned that IL-1 or a similar ancestral cytokine is likely to be present in the invertebrates for several reasons. First, the molecular conservation of IL-1 and its host defense functions have been preserved in the vertebrates. Second, macrophages which produce IL-1 are present throughout the animal kingdom. Echinoderms and urochordates belong to the deuterostomes as do the vertebrates, while all the other invertebrates are members of the protostomes. Results from this laboratory have demonstrated the presence of cytokines in both major groups of invertebrates. The goals of this research are to determine the amino acid and DNA sequences of invertebrate IL-1 and TNF and compare them with those of the vertebrates. The functions of these mediators in the invertebrates will be characterized using starfish systems in vivo and in vitro. %%% The goal of this research is to characterize, in certain key invertebrate animals, chemical regulators (cytokines) of their immune-like defense mechanisms. Study of these invertebrate immune-like defense mechanisms will contribute to understanding of how a wide range of organisms respond to environmental challenges. In addition, investigation of the cytokines of more primitive organisms may help us decipher the complex cellular and humoral interactions of the immune systems of higher animals. ***
