LPS-induced genes and protects mice from lethal endotoxin shock

JEM © The Rockefeller University Press $8.00 Vol. 203, No. 1, January 23, 2006 15–20 www.jem.org/cgi/doi/10.1084/jem.20051753 15 Innate immune cell activation via Toll-like receptors induces the release of infl ammatory cytokines, chemokines, and mediators. A rapid and robust response of macrophages and dendritic cells is needed for the control and elimination of fast-growing microbial invaders. Nevertheless, the intensity and duration of this response have to be limited to avoid excessive infl ammatory tissue damage. A range of regulatory factors acts at multiple levels to restrict or down-regulate the cytokines released from activated macrophages. These include the inhibitory cytokines IL-10 and TGF-β; cytokine antagonists, such as IL-1Rn and IL-18 binding protein; intracellular modulators of signaling pathways, such as the phosphatase SHIP (1); members of the suppressor of cytokine signaling protein family (2); and transcriptional regulators, such as c-maf (3) and Bcl-3 (4). Functionally, LPS-triggered activation of macrophages induces a state of refractoriness to further stimulation, a process termed LPS tolerance