Interleukin 1 (IL 1) is a soluble mediator that promotes several phases of the immune response. Most of our efforts in the past year were devoted to understanding how IL 1 participates in the T cell activation process. This activation process requires that T cells interact with antigen-presenting cells (APC), such as macrophages or B cells, and the prevailing view has been that the APC provides IL 1 to the T cell. Our findings indicated that the opposite occurs with many T cell clones - that B cells cannot produce IL 1, but rather induce its production by the T cell. This unexpected finding has reoriented our perspective of IL 1's role in T cell activation. For some T cell clones, a second mechanism of IL 1 production also occurs during T cell-macrophage interactions. In the best studied case, a T cell clone which was incapable of producing its own IL 1 was observed to induce high levels of IL 1 production by macrophages. This process was mediated by a novel lymphokine and has lead to the description of a new mechanism of T cell-macrophage signalling. Other studies in the laboratory have concerned different aspects of the biology of IL 1 and its role in cancer. First, we have identified a new IL 1 species (distinct from IL 1-alpha and IL 1-beta) in human amniotic fluid, suggesting new roles for IL 1 in fetal ontogeny and parturition. Second, we have identified a macrophage-like tumor (the murine P388D1 line) that both produces IL 1 and proliferates in response to it, suggesting an autocrine role of IL 1 in tumor growth. Lastly, we have established in vivo systems to explore the use of IL 1 as an adjuvant for promoting endogenous anti-tumor immunity. Thus far, most of our strategies have achieved the opposite outcome - IL 1 strongly enhanced the metastatic spread of a melanoma in mice. Understanding how IL 1 promoted tumor growth, as well as continuing to search for means of exploiting IL 1's powerful adjuvant properties to reduce tumor growth will occupy us in the coming year.
