Signal integration, crosstalk mechanisms and networks in the function of inflammatory cytokines.

Infection or cell damage triggers the release of pro-inflammatory cytokines such as interleukin(IL)-1α or β and tumor necrosis factor (TNF)α which are key mediators of the host immune response. Following their identification and the elucidation of central signaling pathways, recent results show a highly complex crosstalk between various cytokines and their signaling effectors. The molecular mechanisms controlling signaling thresholds, signal integration and the function of feed-forward and feedback loops are currently revealed by combining methods from biochemistry, genetics and in silico analysis. Increasing evidence is mounted that defects in information processing circuits or their components can be causative for chronic or overshooting inflammation. As progress in biosciences has always benefitted from the use of well-studied model systems, research on inflammatory cytokines may function as a paradigm to reveal general principles of signal integration, crosstalk mechanisms and signaling networks.