Cytokines are a group of protein molecules that function as the hormones of the immune system to effect the growth and differentiation of a variety of cells. A major effort of my laboratory has been to understand how the cell transmits the signal delivered by the cytokine at the surface to the nucleus of the cell where genes can be turned on that are otherwise dormant. Our lab has shown that interferons and other cytokines initiate a cascade of reactions that ends by the chemical modification of a latent protein referred to as transcription factors that migrate to the nucleus of the cell where they promote the expression of genes involved in inflammation. A multi-molecular complex is formed at the cell surface which isomposed of the receptor, enzymes that transduce the signal from the receptor, and the transcription factor. We have shown that each kinase binds to certain chains of the interferon gamma receptor. We have also shown that the activation of these kinases and transciption factors can be modulated by other cytokines, immune complexes, or tumor promoting agents. The work on-going in my laboratory is directed at understanding how cytokines of various classes activate cells, both of non-immune and immune origin. An understanding of the mechanisms whereby cytokines activate cells in order to induce new genes allows for a more detailed and scientific approach to the review of these products. In addition, since my laboratory has shown that many cytokines share components of their signalling cascade, this helps explain some of the pleiotropic nature of many cytokines and the reasons that toxicities may occur in a number of organ systems and that cummulative toxicities may occur when mutlitple cytokines are used. We have also developed methods that allow us to measure the effects of various cytokines on monocytes and lymphocytes by measuring transcription factor activation. This may provide for a sensitive way to monitor the biodynamic effects on cytokine during treatment protocols. This recently became evident during the observed toxicity of IL-12. Our laboratory was able to quickly assay these samples using signal transduction activation assays in place in the lab.
