The COX- inhibitor indomethacin reduces Th1 effector and T regulatory cells in vitro in Mycobacterium tuberculosis infection

• Published in: BMC infectious diseases 2016-10, Vol.16 (1), p.599-599, Article 599
• Main Authors: Tonby, Kristian, Wergeland, Ida, Lieske, Nora V, Kvale, Dag, Tasken, Kjetil, Dyrhol-Riise, Anne M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Analysis; Antigens, Bacterial - metabolism; Cancer; Care and treatment; Chemotherapy; COX-inhibitors; Cyclooxygenase 2 - blood; Cyclooxygenase Inhibitors - pharmacology; Cytokines - metabolism; Dosage and administration; Drug resistance; Female; Flow Cytometry; Host-directed therapy; Humans; Indomethacin; Indomethacin - pharmacology; Infectious diseases; Latent Tuberculosis - drug therapy; Latent Tuberculosis - microbiology; Latent Tuberculosis - pathology; Male; Middle Aged; Monocytes; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - pathogenicity; Regulatory T cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - microbiology; Th1 Cells - drug effects; Treatment outcome; Tregs; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; Tuberculosis - pathology; Tumor Necrosis Factor-alpha - pharmacology; Young Adult
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-016-1938-8

Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy. COX-2 expression in monocytes and ESAT-6 and Ag85 specific T cell cytokine responses (TNF-α, IFN-γ, IL-2), proliferation (carboxyfluorescein succinimidyl ester staining) and regulation (FOXP3+ T regulatory cells) were analysed by flow cytometry and the in vitro effects of the COX-1/2 inhibitor indomethacin were measured. We demonstrate that indomethacin significantly down-regulates the fraction of Mtb specific FOXP3+ T regulatory cells (ESAT-6; p = 0.004 and Ag85; p