Interleukin 10 responses are associated with sustained CD4 T-cell counts in treated HIV infection.
BACKGROUND
Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non-AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART).


METHODS
A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/μL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2-4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation.


RESULTS
Undetectable HIV RNA (<80 copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation.


CONCLUSIONS
Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.
Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. villacre@usc.edu
Maria C
MC
Villacres
Naoko
N
Kono
Wendy J
WJ
Mack
Marek J
MJ
Nowicki
Kathryn
K
Anastos
Michael
M
Augenbraun
Chenglong
C
Liu
Alan
A
Landay
Ruth M
RM
Greenblatt
Stephen J
SJ
Gange
Alexandra M
AM
Levine
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D016753:Interleukin-10 / Q000276:immunology*; D016014:Linear Models; D015999:Multivariate Analysis; D011446:Prospective Studies; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D012367:RNA, Viral; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D016753:Interleukin-10