Inflammatory mediators, factors affecting

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... 

Corticosteroids (e.g., prednisone, cortisone, dexamethasone) stabilize membranes of leukocytes, decreasing the release of inflammatory mediators, as well as chemotaxic factors. This decreases inflammation and also decreases the influx of leukocytes to the affected area, which further decreases inflammatory tendencies. 

Inhibitors of IkBo phosphorylation have been described which irreversibly inhibit cytokine-induced phosphorylation without affecting constitutive phosphorylation. One such compound (Bay 11-7083 ((E)3-[4-f-butylphenyl)-sulfonyl]-2-propenenitrile)) was found to be effective in two animal models of inflammation after intraperitoneal administration [89]. In addition to the effect it has on the expression of adhesion molecules in pro-inflammatory responses, inhibition of the transcription factor NFkB will also have an effect on angiogenesis. Endothelial cells can produce growth factors and cytokines which have pro-angiogenic effects. Some of these factors, e.g. IL-8, TNFa and MCP-1 are known to be produced via NFkB-mediated endothelial cell activation [90,91]. The importance of NFKB-mediated responses in pro-angiogenic endothelium was reflected in studies in which the NFkB inhibitor PDTC decreased retinal neovascularization in the eye of mice [92]. 

Some authors claim that liposaccharides can depress the content of TNF-a and increase the activity of superoxide dismutase (SOD) and catalase, thus—via mediators—they can affect the immune system (Can et al. 2003). It has been demonstrated that the NF-p transcription factor, (highly sensitive to the redox potential in its environment), which regulates synthesis of many mediators—cytokines, associated with inflammatory condition and the phenomenon of adhesion of cells— becomes deregulated in old age. Defense functions in such cases (and primarily in arthritis and arthritis-related conditions) are said to be performed by antioxidants (including a-lipoic acid), which can modulate the activity of monocytes and inhibit changes caused by deregulating of the transcription factor NF-kB under the influence of redox conditions in elderly people (Lee and Hughes 2002). 

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