title: Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome.
abstract: The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone--which reduces the duration of symptoms in IRIS patients--or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had increased MMP-1, -3, -7, and -10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tadokera
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Meintjes
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Keira H
authors.initials: KH
authors.lastname: Skolimowska
authors.forename: Naomi
authors.initials: N
authors.lastname: Walker
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Paul T G
authors.initials: PT
authors.lastname: Elkington
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D020782:Matrix Metalloproteinases; D011241:Prednisone
keywords: Drug therapy complications; HIV-1 infection; Immune reconstitution inflammatory syndrome; Matrix metalloproteinase; Tuberculosis