Interleukin modulator studies

McGahon B, Murray CA, Clements MP, Lynch MA. Analysis of the effect of membrane arachidonic acid concentration on modulation of glutamate release by interleukin-1 an age-related study. Exp Gerontol 1998 33 343-354. 

A key genetic study, utilizing a knock-in mutation of a dimerization-deficient mutant of GR, has shed light on the molecular basis for dissociative activity [101]. In essence, this GRdim mutant demonstrated that some of the direct gene transduction properties of GR can be reduced while other immune-modulating functions of the receptor can be retained. This concept forms one of the principles of selective modulation of GR. Importantly, many of the anti-inflammatory effects of GR are believed to be driven by the ability of the monomeric form of the receptor to interfere with NF-xB and AP-1 function, which ultimately results in reduction of proinflammatory cytokines such as interleukins (IL)-l, -2, -6, -8, and tumor necrosis factor (TNF) TNFa [69]. 

Thymosins. Thymosins are hormone-like polypeptides produced by thymus epithelial cells. They regulate the maturation of T-cells moreover, they modulate interferon production and stimulate the expression of interleukin-2 and its receptor. A trial of thymosin fraction-5 in four homosexual patients with chronic hepatitis B demonstrated no effect after six months of treatment (202), while treatment of WHV-infected woodchucks with thymosin alpha-1 resulted in clearance of circulating WHV-DNA and a 50-300-fold decline in the levels of replicative intermediates in liver tissue (203). Subsequently, thymosin alpha-1 and thymosin fraction-5 were used to treat chronic hepatitis B in a human pilot study (204). Results were encouraging, and this was followed by several randomized, controlled multicenter trials of thymosin alpha-1 in the U.S. The primary action of thymosin is unknown, but it is probably related to its immune-enhancing effects. 

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