Evan T. Keller^1,2,3, Jon Wanagat¹, W.B. Ershler^1,3

¹Glennan Center for Geriatrics and Gerontology, Departments of ²Pathology and ³Internal Medicine, Eastern Virginia Medical School.

Received 10/21/96; Accepted 11/01/96; On-line //96

6. SUMMARY

IL-6 is active in a great number of physiologic and pathophysiologic processes. A wide variety of factors have been demonstrated to modulate IL-6 expression. While may of these stimulate IL-6 expression, only a few factors have been demonstrated to inhibit IL-6 expression. Among the inhibitors of IL-6 gene expression are steroids, including corticosteroids, estrogen, and androgens. Steroids appear to inhibit IL-6 expression thorugh repressing transcriptional activation of the IL-6 gene. In addition to regulation of IL-6 levels, modulation of IL-6R levels is another mechanism by which IL-6 activity is controlled. Both the soluble and membrane bound form of IL-6R mediate IL-6 activity by stimulating cell signalling through activation of gp130. Even though the importance of the IL-6R for manifestation of IL-6 activity is recognized, the molecular mechanisms by which transcriptional control of the IL-6R gene is achieved have not been reported to date. Future studies aimed at elucidating these mechanisms may contribute to understanding how IL-6 is active in a variety of disorders.