Interleukin 6

Interleukin 6 (interferon, beta 2)
PDB rendering based on 1ALU.
Available structures
1alu, 1il6, 1p9m, 2il6
Identifiers
Symbols	IL6; HGF; BSF2; HSF; IFNB2; IL-6
External IDs	OMIM: 147620 MGI: 96559 HomoloGene: 502
Gene ontology Molecular function • cytokine activity • interleukin-6 receptor binding • protein binding Cellular component • extracellular region • extracellular space Biological process • neutrophil apoptosis • acute-phase response • humoral immune response • cell surface receptor linked signal transduction • cell-cell signaling • positive regulation of cell proliferation • negative regulation of cell proliferation • negative regulation of apoptosis • negative regulation of chemokine biosynthetic process
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3569	16193
Ensembl	ENSG00000136244	ENSMUSG00000025746
UniProt	P05231	Q0PMN1
RefSeq	NM_000600 (mRNA)	NM_031168 (mRNA)
	NP_000591 (protein)	NP_112445 (protein)
Location	Chr 7: 22.73 - 22.74 Mb	Chr 5: 30.34 - 30.35 Mb
PubMed search	[1]	[2]

Interleukin-6 (IL-6) is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. In terms of host response to a foreign pathogen, IL-6 has been shown, in mice, to be required for resistance against the bacterium, Streptococcus pneumoniae^[1]. IL-6 is also a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction^[2]. It is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation. During exercise, it is thought to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery (Petersen, J Appl Physiol 2005). Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory cytokine is mediated through its inhibitory effects on TNF-alpha and IL-1, and activation of IL-1ra and IL-10.

Functions of IL-6

IL-6 is one of the most important mediators of fever and of the acute phase response. In the muscle and fatty tissue IL-6 stimulates energy mobilization which leads to increased body temperature. IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen associated molecular patterns (PAMPs). These PAMPs bind to highly important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production. IL-6 is also essential for hybridoma growth and is found in many supplemental cloning media such as briclone. Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. Il-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP. In a 2009 study, intranasally administered IL-6 was shown to improve sleep-associated consolidation of emotional memories.^[3]

The IL-6 receptor

IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). CD130 is the common signal transducer for several cytokines including leukemia inhibitory factor(LIF), ciliary neurotropic factor, oncostatin M, IL-11 and cardiotrophin-1, and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors, Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs)^[4].

IL-6 is probably the best studied of the cytokines that use gp130 in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma associated herpes virus interleukin 6 like protein (KSHV-IL6).^[5] These cytokines are commonly referred to as the IL-6 like or gp130 utilising cytokines ^[6].

In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth promote survival of neurons, hence may be important in nerve regeneration through remyelination.

Interactions

Interleukin 6 has been shown to interact with Interleukin-6 receptor.^[7][8][9]

References

Further reading

v • d • e PDB Gallery 1alu: HUMAN INTERLEUKIN-6   1il6: HUMAN INTERLEUKIN-6, NMR, MINIMIZED AVERAGE STRUCTURE   1p9m: Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex   2il6: HUMAN INTERLEUKIN-6, NMR, 32 STRUCTURES