Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

Abstract

Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.

Oxidative stress stimulates IL‐4 and IL‐6 production in mast cells by an APE/Ref‐1‐dependent pathway

“…IL-6 relates to a proinflammatory response, which may result from free radical generation as a part of the inflammatory response [30]. Nevertheless there are no suggestions in the literature for a role of oxidative microenvironment on IL-6 production from mast cells.…”

Stimulation of Leukemia Inhibitory Factor Receptor Degradation by Extracellular Signal-regulated Kinase

“…LIF, and related cytokines, are involved in the regulation of hematopoiesis, immune response, inflammatory processes, bone and muscle remodeling, neural development, kidney differentiation, and mammalian reproduction (1)(2)(3)(4)54). Our study suggests that not only are levels of IL-6 cytokines important, but also the specific restriction of cytokine responsiveness by modulated receptor subunit levels.…”

Endogenous leukemia inhibitory factor attenuates endotoxin response

“…3 A partial functional redundancy of LIF with IL-6, IL-11, ciliary neutrotrophic factor (CNTF) and oncostatin M (OSM) is due to the fact that all these ligands utilize the common receptor subunit gp130, together with their specific receptors. [4][5][6] LIF can be induced by TNFa, IL-1 and LPS, and is expressed by a variety of cell types in vitro, including fibroblasts, activated T cells, monocytes, macrophages, bone marrow stromal cells, astrocytes and endothelial cells, as well as by a number of tissues in adults. 4,7 Clinical studies demonstrated that serum concentrations of LIF are elevated in patients with Gram-negative and meningococcal septic shock 8 and that the levels correlated with the severity of disease.…”