Birx D L, Lewis M G, Vahey M, Tencer K, Zack P M, Brown C R, Jahrling P B, Tosato G, Burke D, Redfield R
Department of Retroviral Research, Walter Reed Army Institute of Research, Rockville, Maryland 20850.
AIDS Res Hum Retroviruses. 1993 Nov;9(11):1123-9. doi: 10.1089/aid.1993.9.1123.
Infection with a variant of simian immunodeficiency virus (SIVsmm/PBj-14) causes death in juvenile pigtailed macaques within 8 days of infection. The primary pathology is localized to the lymphoid tissues of the gut and spleen. Although the virus is present, the lesions are most consistent with acute reactive inflammation. We studied the serum and tissues for evidence of acute cytokine production often associated with acute inflammation. One factor, IL-6, was found to be significantly increased (> 1000-fold) over all other measured cytokines in all the pigtailed macaques who died acutely. Increased levels of IL-6 were found both in the serum and in the inflamed tissues. mRNA for IL-6 was found in the tissues with the highest protein levels of IL-6. The marked increase in IL-6 and IL-6 mRNA correlated with the virus levels in the tissues and serum as determined by viral isolation, immunohistochemistry, and Northern blot analysis. These findings suggest that the underlying pathogenesis of primary tissue damage, necrosis, and death by PBj-14 is the induction of cytokine production. Although the presence of the virus may be critical for the initiation of these events, the intense inflammatory reaction is associated with the cause of death.
感染猿猴免疫缺陷病毒（SIVsmm/PBj - 14）的一种变体，会在幼年猪尾猕猴感染后的8天内导致其死亡。主要病理变化局限于肠道和脾脏的淋巴组织。尽管存在病毒，但病变最符合急性反应性炎症。我们研究了血清和组织，以寻找通常与急性炎症相关的急性细胞因子产生的证据。在所有急性死亡的猪尾猕猴中，发现一种细胞因子白细胞介素 - 6（IL - 6）比所有其他检测的细胞因子显著增加（超过1000倍）。在血清和发炎组织中均发现IL - 6水平升高。在IL - 6蛋白水平最高的组织中发现了IL - 6的mRNA。通过病毒分离、免疫组织化学和Northern印迹分析确定，IL - 6和IL - 6 mRNA的显著增加与组织和血清中的病毒水平相关。这些发现表明，PBj - 14导致原发性组织损伤、坏死和死亡的潜在发病机制是细胞因子产生的诱导。尽管病毒的存在可能对这些事件的启动至关重要，但强烈的炎症反应与死亡原因相关。
