Hasan Z, Mahmood A, Zafar S, Khan A A, Hussain R
Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan.
Int J Lepr Other Mycobact Dis. 2004 Mar;72(1):35-44. doi: 10.1489/1544-581X(2004)072<0035:LPWLDH>2.0.CO;2.
Tumor necrosis factor (TNF-alpha) in conjunction with interferon-gamma (IFN-gamma) plays an important role in lymphocyte recruitment and granuloma formation in mycobacterial diseases. Lepromatous leprosy infections are typically associated with low to absent T cell responses and the absence of INF-gamma secretion. Chemokines such as IL-8, MCP-1, and MIP-1beta, have also been shown to recruit neutrophils and lymphocytes to the site of mycobacterial infections. We have studied IL-8 expression in relation to TNF-alpha and TGF-beta in monocytes from lepromatous patients (LL) as compared with healthy endemic controls. In endemic controls, no spontaneous expression of IL-8, TNF-alpha, and TGF-beta was observed, but BCG and M. leprae induced activation of all three cytokines. Lepromatous leprosy monocytes spontaneously expressed high levels of IL-8 and TGF-beta but negligible levels of TNF-alpha. A further increase in IL-8 secretion or gene expression by BCG or M. leprae was not significant. BCG, but not M. leprae, was able to stimulate TNF-alpha activation in lepromatous leprosy subjects. TGF-beta responses in LL were parallel to those of IL-8. This suggests a vigorous and active ongoing IL-8 response in lepromatous disease that is independent of TNF-alpha activation. Therefore, in the absence of IFN-gamma and TNF-alpha activation, IL-8 may assume a pivotal role in cell recruitment in leprosy patients with disseminated mycobacterial infections.
肿瘤坏死因子（TNF-α）与干扰素-γ（IFN-γ）共同作用，在分枝杆菌病的淋巴细胞募集和肉芽肿形成中发挥重要作用。瘤型麻风感染通常与低水平或缺乏T细胞反应以及缺乏INF-γ分泌有关。趋化因子如IL-8、MCP-1和MIP-1β也已被证明可将中性粒细胞和淋巴细胞募集到分枝杆菌感染部位。我们研究了瘤型麻风患者（LL）单核细胞中IL-8的表达与TNF-α和TGF-β的关系，并与健康的流行区对照进行比较。在流行区对照中，未观察到IL-8、TNF-α和TGF-β的自发表达，但卡介苗和麻风杆菌可诱导所有这三种细胞因子的激活。瘤型麻风单核细胞自发表达高水平的IL-8和TGF-β，但TNF-α水平可忽略不计。卡介苗或麻风杆菌进一步增加IL-8分泌或基因表达并不显著。卡介苗能刺激瘤型麻风患者的TNF-α激活，但麻风杆菌不能。LL中TGF-β的反应与IL-8平行。这表明在瘤型麻风病中存在活跃且持续的IL-8反应，且该反应独立于TNF-α激活。因此，在缺乏IFN-γ和TNF-α激活的情况下，IL-8可能在播散性分枝杆菌感染的麻风患者的细胞募集中起关键作用。
