Inflammatory mediators interleukin

CD C14 C14.001 Caspase-1 Potential drug target for down-regulation of the inflammatory mediator, interleukin 1beta, which could ameliorate inflammation and endotoxic shock... 

A number of diflFerent animal models of uveitis have been developed) including that induced by organ-specific ocular antigens such as retinal S-antigen, rhodopsin and lens protein (Wacker et al., 1977 Rao et al., 1979). Other models are based on the injection of proteins foreign to the host, such as intravitreal injections of albumin or 7-globulin (Zimmerman and Silverstein, 1959 Kaplan etal., 1979). More recently, a third group of models has been developed based on the injection of inflammatory mediators such as interleukins-1 and 2, and tumour necrosis factor (Bhattacherjee and Henderson, 1987 ... 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Endotoxaemia. - Exposure to bacterial endotoxin (lipopolysaccharide) can induce the production of pro-inflammatory mediators (e.g. tumour necrosis factor a and interleukin 1), culminating in septic shock profound vasodilation... 

L3. Lapteva, N., Ando, Y., Nieda, M., Hohjoh, H., Okai, M., Kikuchi, A., Dymshits, G., Ishikawa, Y., Juji, T., and Tokunaga, K., Profihng of genes expressed in human monocytes and monocyte-derived dendritic cells using cDNA expression array. Br. J. Haematol. 114, 191-197 (2001). L4. Lauw, F. N., Dekkers, P. E., te Velde, A. A., Speelman, P., Levi, M., Kurimoto, M., Hack, C. E., van Deventer, S. J., and van der Poll, T., Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. J. Infect. Dis. 179,646-652 (1999). 

TCDD inhibits the terminal differentiation of B cells via alteration of an early activation event, perhaps increased protein phosphorylation and tyrosine kinase activity (Clark et al. 1991a Kramer et al. 1987 Luster et al. 1988 Morris et al. 1991). Macrophage functions, examined ex vivo, generally have been found to be resistant to suppression by 2,3,7,8-TCDD (Mantovani et al. 1980 Vos et al. 1978). There is also evidence suggesting that inflammatory cells may be activated by 2,3,7,8-TCDD via enhanced production of inflammatory mediators such as interleukin 1 and tumor necrosis factor (Clark et al. 1991b Taylor etal. 1992). 

One study examining the inflammatory mediators revealed that compared with normal skin, prostaglandin E2 was increased approximately 3.8-fold (p <. 0002) in sensitive skin compared to normal skin. Leukotriene B4 and interleukin-1 showed no differences between normal and sensitive skin individuals.35 Progress has been made in establishing the pathophysiology of sensitive skin however, a great deal of work remains to be done in this field. 

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