Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome
Faculty of Medicine and Health Sciences
Clinical infectious diseases. - Chicago, Ill.
, p. 1004-1011
University of Antwerp
Background. Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Methods. Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH) D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. Results. Patients prescribed concurrent CTC had lower interferon gamma (IFN-gamma), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P <= .02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P <= .04) of ART. Vitamin D deficiency (total 25(OH) D <75 nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH) D decreased during 2 weeks (P = .004) of ART. Severe vitamin D deficiency (total 25(OH) D <25 nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. Conclusions. CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.