Tadokera, Rebecca ORCID: https://orcid.org/0000-0001-5195-2376, Meintjes, G., Skolimowska, K.H., Wilkinson, K.A., Matthews, K., Seldon, R., Chegou, N.N., Maartens, G., Rangaka, M.X., Rebe, K., Walzl, G. and Wilkinson, R.J. (2010) Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. The European respiratory journal, 37 (5). pp. 1248-1259.

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Abstract

Increased 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.

Item Type:	Article
Status:	Published
DOI:	https://doi.org/10.1183/09031936.00091010
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/9380

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