Stadler I, Chadha K C, Nakeeb S, Toumbis C, Butsch J, Mathur N, Munschauer F, Vladutiu A, Satchidanand S K, Ambrus J L
Department of Internal Medicine, Buffalo General Hospital, State University of New York.
J Pharmacol Exp Ther. 1994 Jan;268(1):10-3.
C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (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 previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through 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) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.
感染LP - BM5 MuLV病毒的C57/BL/6小鼠患上了一种类似艾滋病的疾病（MAIDS），出现脾肿大、白细胞减少、血小板减少、贫血、辅助/诱导性T细胞和抑制/细胞毒性T细胞数量减少以及α干扰素产生减少的症状。我们之前已经表明，与HIV相关的卡波西肉瘤组织中含有高水平的前列腺素E2（PgE2），并且它通过一种依赖cAMP的第二信使过程抑制干扰素合成。在本研究中，我们用己酮可可碱（一种增加cAMP并抑制磷酸二酯酶的药物）和甲氯芬那酸钠（一种PgE2抑制剂）的组合对感染MAIDS的小鼠组进行治疗。接受治疗的小鼠表现出：1）白细胞和血小板总数显著更高，2）L3T4 +（辅助/诱导性）和Lyt - 2 +（抑制 - 细胞毒性）T细胞总数更高。病理检查还显示，用己酮可可碱和甲氯芬那酸钠治疗的动物肝脾肿大和淋巴结病明显减轻。在这种艾滋病小鼠模型中，部分由PgE2诱导的α干扰素产生抑制可能介导了逆转录病毒感染的表达。
