• R Tadokera, G Meintjes, K H Skolimowska, K A Wilkinson, K Matthews, R Seldon, N N Chegou, G Maartens, M X Rangaka, K Rebe, G Walzl, and R J Wilkinson.
• Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
• Eur. Respir. J. 2011 May 1; 37 (5): 1248-59.

AbstractIncreased access to combination antiretroviral therapy in areas co-endemic for tuberculosis (TB) and HIV-1 infection is associated with an increased incidence of immune reconstitution inflammatory syndrome (TB-IRIS) whose cause is poorly understood. A case-control analysis of pro- and anti-inflammatory cytokines in TB-IRIS patients sampled at clinical presentation, and similar control patients with HIV-TB prescribed combined antiretroviral therapy who did not develop TB-IRIS. Peripheral blood mononuclear cells were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 h. Stimulation with M. tuberculosis increased the abundance of many cytokine transcripts with interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-13, IL-17A, interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF) being greater in stimulated TB-IRIS cultures. Analysis of the corresponding proteins in culture supernatants, revealed increased IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p40, IFN-γ, GM-CSF and TNF in TB-IRIS cultures. In serum, higher concentrations of TNF, IL-6, and IFN-γ were observed in TB-IRIS patients. Serum IL-6 and TNF decreased during prednisone therapy in TB-IRIS patients. These data suggest that cytokine release contributes to pathology in TB-IRIS. IL-6 and TNF were consistently elevated and decreased in serum during corticosteroid therapy. Specific blockade of these cytokines may be rational approach to immunomodulation in TB-IRIS.

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