Interferon interleukin-12 production regulation

Biomedical research continues to broaden our understanding of the molecular mechanisms underlining both health and disease. Research undertaken since the 1950s has pinpointed a host of proteins produced naturally in the body that have obvious therapeutic applications. Examples include the interferons and interleukins (which regulate the immune response), growth factors, such as erythropoietin (EPO which stimulates red blood cell production), and neurotrophic factors (which regulate the development and maintenance of neural tissue). 

Fantuzzi G, Puren AJ, Harding MW, Livingston DJ, Dinarello CA. Interleukin-18 regulation of interferon gamma production and cell proliferation as shown in interleukin-1 beta-converting enzyme (caspase-l)-deficient mice. Blood 1998 91 2118-2125. 

Lepe-Zunga, J. L., and Klostergaard, J. (1990). Tolerance to endotoxin in vitro Independent regulation of interleukin-1, tiunor necrosis factor and interferon alpha production during in vitro differentiation of human monocytes. Lymphokine Res. 9, 309-319. 

Osteoclasts are multinucleated cells found on the endosteal surface of bone, in Haversian systems and periosteal surfaces. PTH activates osteoclasts (indirectly via osteoblasts that possess PTH receptors). Calcitonin is a potent inhibitor of osteoclast activity. Local cytokine factors, including interleukin-1 (IL-1), tumour-necrosis factor (TNF), TGF- 0 and interferon-y (INF-y), are important regulators. Osteoclast resorption of bone releases collagen peptides, pyridinoline cross-links and calcium from the bone matrix, through the action of lysosomal enzymes (collagenases and cathepsins). The collagen breakdown products in serum and urine (e.g. hydroxyproline) can be used as biochemical markers. 

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. 

A variety of immune system products (cytokines, peptides) that function to coordinate the immune response may provide important signals for the neuroendocrine system. Those, currently known to have the most relevance for the neuroendocrine system are interleukins (IL) IL-1, IL-2, IL-6, tumour necrosis factors (TNF) and the interferons (IFN) their major role lies in the physiology of inflammation (infection, tumour growth). Lymphokines enhance the release of dopamine and norepinephrine from the adrenal medulla, the dopamine turnover in the brain and serve as endogeneous neurokines regulating striatal dopaminergic function (Zalcman et ah, 1994). Similarly, the dopamine is involved in the modulation of both TNFa and nitric oxide production by peritoneal macrophages, IL-6 release and inhibition of the TNFa synthesized by adrenal cells (Ritchie et al., 1996). 

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