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.
N1 - Funding Information:
Financial support. This work was supported by the National Institutes of Health (grant U01HD032632 to A. M. L. and grant R03 AI076011to M. C. V.) and the Zumberge Foundation of the University of Southern California (to M. C. V.). Potential conflicts of interest. All authors: No reported conflicts.
Funding Information:
Acknowledgments. Data in this manuscript were collected at the WIHS Collaborative Study Group centers (principal investigators): New York City/ Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131).
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 -