Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome.

Abstract

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 γ (IFN-γ), 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.

• Authors: Anali Conesa-Botella, Graeme Meintjes, Anna K Coussens, Helen van der Plas, Rene Goliath, Charlotte Schutz, Rodrigo Moreno-Reyes, Meera Mehta, Adrian R Martineau, Robert J Wilkinson, Robert Colebunders, Katalin A Wilkinson
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 55 Issue 7 Pg. 1004-11 (Oct 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22715179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Cytokines
• Immunologic Factors

Topics

• Adrenal Cortex Hormones (administration & dosage)
• Adult
• Cytokines (blood)
• Female
• HIV Infections (complications, drug therapy, pathology)
• Humans
• Immune Reconstitution Inflammatory Syndrome (pathology)
• Immunologic Factors (administration & dosage)
• Male
• Prospective Studies
• Tuberculosis (complications, pathology)
• Vitamin D Deficiency (epidemiology)