Leprosy patients with lepromatous disease have an up-regulated IL-8 response that is unlinked to TNF-α responses

Tumor necrosis factor (TNF-α) in conjunction with interferon-γ (IFN-γ) 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-γ secretion. Chemokines such as IL-8, MCP-1, and MIP-1β, 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-α and TGF-β in monocytes from lepromatous patients (LL) as compared with healthy endemic controls. In endemic controls, no spontaneous expression of IL-8, TNF-α, and TGF-β 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-β but negligible levels of TNF-α. 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-α activation in lepromatous leprosy subjects. TGF-β 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-α activation. Therefore, in the absence of IFN-γ and TNF-α activation, IL-8 may assume a pivotal role in cell recruitment in leprosy patients with disseminated mycobacterial infections.