An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses
| Autor: | Andreas Lind, Eirik A. Torheim, Dag Kvale, Frank Olav Pettersen, Ingeborg S. Aaberge, Malin Holm, Per Morten Sandset, Kjetil Taskén, Einar Martin Aandahl, Anders E.A. Dahm |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male T-Lymphocytes CD3 T cell Immunology Down-Regulation HIV Infections Biology CD38 Microbiology Virology medicine Humans IL-2 receptor Interleukin-7 receptor AIDS Vaccines Sulfonamides Cyclooxygenase 2 Inhibitors Middle Aged Treatment Outcome medicine.anatomical_structure Celecoxib Insect Science Chronic Disease Disease Progression HIV-1 biology.protein Pyrazoles Pathogenesis and Immunity Female Cyclooxygenase CD8 medicine.drug |
| Zdroj: | Journal of Virology. 85:6557-6566 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00073-11 |
| Popis: | Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E 2 following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial. Thirty-one patients were randomized in the trial; 27 completed the study, including 13 patients on celecoxib. Celecoxib reduced chronic immune activation in terms of CD38 density on CD8 + T cells (−24%; P = 0.04), IgA levels ( P = 0.04), and a combined score for inflammatory markers ( P < 0.05). Celecoxib further reduced the inhibitory surface receptor programmed death 1 (PD-1) on CD8 + T cells ( P = 0.01), including PD-1 on the HIV Gag-specific subset ( P = 0.02), enhanced the number of CD3 + CD4 + CD25 + CD127 lo/− Treg or activated cells ( P = 0.02), and improved humoral memory recall responses to a T cell-dependent vaccine ( P = 0.04). HIV RNA ( P = 0.06) and D dimers ( P = 0.07) tended to increase in the controls, whereas interleukin-6 (IL-6) possibly decreased in the treatment arm ( P = 0.10). In conclusion, celecoxib downmodulated the immune activation related to clinical progression of chronic HIV infection and improved T cell-dependent functions in vivo . |
| Databáze: | OpenAIRE |
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