Minocycline protects macaques from SIV-encephalitis and is immunomodulatory in SIV-infected macaques

World Health Organization figures indicate that in 2003 over 40 million adults and children were infected with HIV globally. Current anti-AIDS therapies are expensive, require complex dosing regimens with significant side effects and toxicity and do not readily cross the blood brain barrier. We recently demonstrated that minocycline, a safe, readily available, inexpensive, semisynthetic tetracycline derivative prevented the development of SIV encephalitis in macaques. Minocycline-treated macaques had lower levels of viral RNA in the brain and lower numbers of lymphocytes and macrophages infiltrating the brain. These findings prompted us to examine the potential effects of minocycline on the immune system of SIV-infected macaques, and in particular, the potential effects of minocycline on T lymphocyte proliferation, function, and homing capabilities in macaque primary blood lymphocytes in vitro. Our studies demonstrated that minocycline inhibited T cell proliferation and activation, down-regulated CCR5 expression, reduced cell surface LFA-1 expression and reduced loss of CD45RA after SEB stimulation. Other in vitro studies have suggested that minocycline decreased production of certain cytokines, including IL-2, IFN-(gamma), and TNF-(alpha). These findings suggest that the therapeutic effect of minocycline is likely associated with down-regulation of CD4+ T cell turnover and decreasing susceptibility of CD4+ T cells to infection by SIV.