Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome.
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.
Clinical Infectious Diseases Research Initiative,  Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory,  South Africa.
Anali
A
Conesa-Botella
Graeme
G
Meintjes
Anna K
AK
Coussens
Helen
H
van der Plas
Rene
R
Goliath
Charlotte
C
Schutz
Rodrigo
R
Moreno-Reyes
Meera
M
Mehta
Adrian R
AR
Martineau
Robert J
RJ
Wilkinson
Robert
R
Colebunders
Katalin A
KA
Wilkinson
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000473:pathology*; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D011446:Prospective Studies; D014376:Tuberculosis / Q000150:complications* / Q000473:pathology; D014808:Vitamin D Deficiency / Q000453:epidemiology*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007155:Immunologic Factors