title: Leprosy patients with lepromatous disease have an up-regulated IL-8 response that is unlinked to TNF-alpha responses.
abstract: 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.
authors.affiliation: Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan. zahra.hasan@aku.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Hasan
authors.forename: A
authors.initials: A
authors.lastname: Mahmood
authors.forename: S
authors.initials: S
authors.lastname: Zafar
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Hussain
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis* / Q000235:genetics; D015440:Leprosy, Lepromatous / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D009163:Mycobacterium bovis; D009166:Mycobacterium leprae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha