Interleukins types

Vigers, G.P.A., et al. Crystal structure of the type-1 interleukin-1 receptor complexed with interleukin-ip. Nature 386 190-194, 1997. 

Recombinant human DL-1 receptor antagonist (Anakinra, Kineret ) blocks the biological activity of interleukin-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Thereby it reduces the pro-inflammatory activities of IL-1 including cartilage destiuction and bone resorption. Side effects include an increased risk of infections and neutropenia. 

Dumoutier L, Tounsi A, Michiels T, Sommereyns C, Kotenko SV, Renauld JC (2004) Role of the interleukin (lL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of lL-29/interferon-lambda 1 similarities with type I interferon signaling. J Biol Chem 279 ... 

Murphy TL, Murphy KM, Weaver CT Interleukin-17-producing CD4+ effector T cells develop via a lineage distinct from the T-helper type 1 and 2 lineages. Nat Immunol 2005 6 1123-1132. 

Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin- 10-treated dendritic cells and transforming growth factor-p for their induction. Clin Exp Allergy 2006 36 1546-1555. 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Clubb RT, Omichinski JG, Clore GM, Gronenbom AM. Mapping the binding surface of interleukin-8 complexes with an N-terminal fragment of the type 1 human interleukin-8 receptor. FEBS Lett 1994 338 93-7. 

Joosten LA, Lubberts E, Helsen MM, et al. Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. Arthritis Res 1999 1(1) 81—91. 

Kasama T, Stricter RM, Lukacs NW, Lincoln PM, Burdick MD, Kunkel SL. Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 1995 95(6) 2868-2876. 

Morohashi H, Miyawaki T, Nomura H, et al. Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells. J Leukoc Biol 1995 57(1) 180-187. 

Interleukin-6 (IL-6) is a small polypeptide with a molecular mass of 26 kDa (see Table 2). IL-6 can be induced in various cell types, including fibroblasts, macrophages/monocytes, epithelial cells, T cells, B cells, and diverse tumor cells (L4). TNF, IL-1, and LPS can stimulate IL-6 gene expression in macrophages/monocytes and fibroblasts. In vivo studies showed that systemic administration of TNF, LPS, and IL-1 was followed by a rapid induction of circulating IL-6 (B49, J2). Also, endothelin (ET) at concentrations observed pathophysiolog-ically may trigger production of IL-6 (Ml7). 

Fujimori, K, et at (2003). Regulation of lipocalin-type prostaglandin D synthase gene expression by Hes-1 through E-box and interleukin-1 beta via two NF-kappa B elements in rat leptomeningeal cells. ]. Biot Chem. 278, 6018-26. 

McKenzie, G.J., Fallon, P.G., Emson, C.L., Grencis, R.K. and McKenzie, A.N.J. (1999) Simultaneous disruption of interleukin (IL)-4 and ILrl3 defines individual roles in T helper type-2-mediated responses. Journal of Experimental Medicine 189,1565-1572. 

Artis, D., Humphreys, N.E., Bancroft, A.J., Rothwell, N.J., Potten, C.S. and Grencis, R.K. (1999a) Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection. Journal of Experimental Medicine 190, 953-962. 

Boirivant, M., Fuss, I.J., Chu, A. and Strober, W. (1998) Oxazolone colitis a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. Journal of Experimental Medicine 188, 1929-1939. 

Iijima, H., Takahashi, I., Kishi, D., Kim, J.K., Kawano, S., Hori, M. and Kiyono, H. (1999) Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice. Journal of Experimental Medicine 190, 607-615. 

Pearlman, E., Lass,J.H., Bardenstein, D.S., Kopf, M., Hazlett, F.E. Jr, Diaconu, E. and Kazura, J.W. (1995) Interleukin 4 and T helper type 2 cells are required for development of experimental onchocercal keratitis (river blindness). Journal of Experimental Medicine 182, 931—940. 

---