PENTOXIFYLLINE AND MECLOFENAMIC ACID TREATMENT REDUCES CLINICAL MANIFESTATIONS IN A MURINE MODEL OF AIDS

C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like d isease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia , decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previousl y that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis throug h a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) signific antly higher total leukocyte and platelet counts, 2) higher total L3T4 + (helper/inducer) and Lyt-2(+) (suppressor/cytoxic) T-cell population . Pathologic examination also showed significantly less hepatosplenome galy and lymphadenopathy in animals treated with pentoxifylline and me clofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this muri ne model of AIDS.