TY - JOUR
T1 - Interleukin 10 responses are associated with sustained CD4 T-Cell counts in treated HIV infection
AU - Villacres, Maria C.
AU - Kono, Naoko
AU - MacK, Wendy J.
AU - Nowicki, Marek J.
AU - Anastos, Kathryn
AU - Augenbraun, Michael
AU - Liu, Chenglong
AU - Landay, Alan
AU - Greenblatt, Ruth M.
AU - Gange, Stephen J.
AU - Levine, Alexandra M.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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/L; 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 1 (IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor (TNF-) 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-1, IL-6, IL-12, and TNF-) 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.
AB - 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/L; 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 1 (IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor (TNF-) 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-1, IL-6, IL-12, and TNF-) 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.
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U2 - 10.1093/infdis/jis380
DO - 10.1093/infdis/jis380
M3 - Article
C2 - 22693231
AN - SCOPUS:84864959547
SN - 0022-1899
VL - 206
SP - 780
EP - 789
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -