Inhibition of inflammation

Dona, M. et al., Neutrophil restraint by green tea Inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis, J Immunol, 170, 4335, 2003. 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

As an oral retinoid, isotretinoin is the most effective sebosuppressive agent that affects all of the etiologic factors involved in inflammatory acne, including induction of atrophy of the sebaceous gland with decreased sebum production and change in sebum composition, inhibition of P. acnes growth within foflicles, inhibition of inflammation, and altered patterns of keratinization within follicles (decreased size and increased differentiation). " These characteristics make it the treatment of choice in severe nodulocystic acne. It may be used... 

Ray, C.A., Black, R.A., Kronheim, S.R., Greenstreet, T.A., Sleath, RR., Salvesen, G.S. and Pickup, D.J. (1992) Viral inhibition of inflammation cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69 597-604. 

Superoxide dismutase Inhibition of cell proliferation Inhibition of inflammation Induction of cell-cycle arrest Induction of apoptosis Inhibition of signal transduction pathways Antiangiogenesis... 

Factors possibly involved in such inhibition of inflammation... 

Bielekova B, Howard T, Packer AN, Richer N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 2009 66(4) 483-9. 

Montesinos MC, Desai A, Delano D, et al. Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum 2003 48 240-247. 

Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

In addition, the alkaloid colchicine (from Colchicum autumnale) blocks tubulin polymerization by binding to heterodimeric (3-tubulin between amino acids 239 and 254. Since it inhibits the MT-dependent migration of granulocytes into areas of inflammation and their MT-dependent release of proinflammatory agents, it is used to treat attacks of gout. Its antimitotic effect in the gastrointestinal system induces diarrhoea. Nocodazole competes for the binding site of colchicine and has similar effects on heterodimeric (3-tubulin. 

Prostaglandins are a group of lipid autacoids known as eicosanoids. They are produced from membrane phospholipids and found in almost every tissue and body fluid. They are involved in a number of physiological processes including inflammation, smooth muscle tone and gastrointestinal secretion. In the central nervous system they have been reported to produce both excitation and inhibition of neuronal activity. 

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