Interleukin-1 Family of Cytokines and Cancer.

The interleukin (IL)-l extended family (IL-lFx) of beta trefoil cytokines now includes a total of 11 members, many of which have been identified as being produced by dendritic cells (DC)s and acting on natural killer (NK) and T-cells. Their major role in immunity remains not fully explored but based on expression data and studies done over the last two decades it is expected that they are important for the initial critical events in NK cell/DC and T-cell/DC interactions, serving as cytokine danger signals or Signal Os alerting the host to damage or injury. They are likely important, following the delivery of antigen/MHC Signal 1 and B7/CD28 Signal 2s during polarization (Signal 3) of the immune response and during the effector phase, as potential Signal 4s associated with tissue specific signaling and homing, driving either inflammation or healing and the fibroblastic response, mediated by IL-Iβ during the effector phase of the immune response as Signal 5s (1,2). Alternatively they deliver activation signals across the immunologie synapse to T-cells and NK cells (3-9). A careful analysis of these factors and their role in NK cell/DC cross talk has not been performed, although analysis of these individual dendrikines in murine models and in vitro human studies suggest that at least IL-18 and a novel factor, IL-lF7b may play important antitumor roles. We will carefully extend observations with these IL-Is to other family members (IL-lFx), determine how they and their inhibitors regulate NK/DC interactions, and promote the adaptive immune response to tumor. [ABSTRACT FROM AUTHOR]