Traditional therapies: glucocorticoids, XXXX , @entity1499 , @entity1862 .

@entity32 @entity859 @entity500 @entity1862 @entity310 @entity51838 @entity134 @entity1178 @entity1499
The 'old favourites' used for treatment of @entity32 , and hence, the original immunomodulators, include the glucocorticoids, @entity500 , @entity1499 and @entity1862 . Glucocorticoids are still one of the most effective anti-inflammatory agents because they work on several different intracellular processes and hence, block many components that contribute to inflammatory and immune responses. They bind to intracellular glucocorticoid receptors which transport them into the nucleus. Here the receptor/ @entity134 complex may bind to many genes that interact with transcription factors including NFkappaB and @entity1178 , to inhibit their activation, thereby preventing activation of many genes encoding immune effector and pro-inflammatory cytokines. Also, protein kinases involved in intracellular signalling, are directly activated resulting in phosphorylation of various targets of which Annexin ( @entity51838 is critical in inhibiting biosynthesis of both purines and DNA. This results in reduced proliferation of B and T lymphocytes, reduced immune effector mechanisms and reduced recruitment of mononuclear cells including monocytes into sites of immune @entity32 . @entity1499 also blocks DNA synthesis and hence cellular proliferation but also induces release of @entity859 . This inhibits chemotaxis of polymorph neutrophils and release of critical cytokines such as @entity310 and Interleukins 6 and 8. @entity1862 also inhibits DNA synthesis with inhibitory effects on proliferation of lymphocytes and possibly kerationcytes. Even though many new agents with much greater selectivity are coming through into clinical use, this group of old agents still have an absolutely central position in the therapeutic armamentarium. Their value lies in the fact that they are not 'clean' drugs with narrow effects but they inhibit a wide range of mechanisms involved in immune and inflammatory processes.
