OBJECTIVE: Increased plasma IL-6 levels have been associated with HIV-1 disease progression risk, yet the drivers of IL-6 production in HIV-1 infection are not known. This study was designed to explore the relationship between HIV-1 replication and IL-6 induction. DESIGN: Correlations between plasma levels of IL-6 and HIV-1 RNA were examined in 2 clinical studies. To more directly assess the induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1 replication in vivo were infected with HIV-1, and expression of IL-6 was measured. METHODS: Spearman rank correlations were used to examine the relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages and colonic and lymph node histocultures were infected with HIV-1 or stimulated with bacterial products, lipopolysaccharide (LPS) or flagellin, and IL-6 levels in supernatant were measured by enzyme-linked immunosorbent assay or multiplex bead assay. RESULTS: In the clinical studies, there was weak or no correlation between plasma levels of IL-6 and HIV-1 RNA, but IL-6 levels were correlated with plasma levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin showed robust production of IL-6, but there was no increase in IL-6 production after HIV-1 infection. IL-6 expression was not increased in lymph node histocultures obtained from HIV-1-infected subjects nor after productive HIV-1 infection of colonic or lymph node histocultures ex vivo. CONCLUSIONS: We find no evidence that HIV-1 replication is an important driver of IL-6 expression in vivo or in in vitro systems.
OBJECTIVE: Increased plasma IL-6 levels have been associated with HIV-1 disease progression risk, yet the drivers of IL-6 production in HIV-1 infection are not known. This study was designed to explore the relationship between HIV-1 replication and IL-6 induction. DESIGN: Correlations between plasma levels of IL-6 and HIV-1 RNA were examined in 2 clinical studies. To more directly assess the induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1 replication in vivo were infected with HIV-1, and expression of IL-6 was measured. METHODS: Spearman rank correlations were used to examine the relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages and colonic and lymph node histocultures were infected with HIV-1 or stimulated with bacterial products, lipopolysaccharide (LPS) or flagellin, and IL-6 levels in supernatant were measured by enzyme-linked immunosorbent assay or multiplex bead assay. RESULTS: In the clinical studies, there was weak or no correlation between plasma levels of IL-6 and HIV-1 RNA, but IL-6 levels were correlated with plasma levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin showed robust production of IL-6, but there was no increase in IL-6 production after HIV-1 infection. IL-6 expression was not increased in lymph node histocultures obtained from HIV-1-infected subjects nor after productive HIV-1 infection of colonic or lymph node histocultures ex vivo. CONCLUSIONS: We find no evidence that HIV-1 replication is an important driver of IL-6 expression in vivo or in in vitro systems.
Authors: Colette Smith; Caroline A Sabin; Jens D Lundgren; Rodolphe Thiebaut; Rainer Weber; Matthew Law; Antonella d'Arminio Monforte; Ole Kirk; Nina Friis-Moller; Andrew Phillips; Peter Reiss; Wafaa El Sadr; Christian Pradier; Signe W Worm Journal: AIDS Date: 2010-06-19 Impact factor: 4.177
Authors: Robert C Kalayjian; Rhoderick N Machekano; Nesrine Rizk; Gregory K Robbins; Rajesh T Gandhi; Benigno A Rodriguez; Richard B Pollard; Michael M Lederman; Alan Landay Journal: J Infect Dis Date: 2010-06-15 Impact factor: 5.226
Authors: A Lafeuillade; I Poizot-Martin; R Quilichini; J A Gastaut; S Kaplanski; C Farnarier; J L Mege; P Bongrand Journal: AIDS Date: 1991-09 Impact factor: 4.177
Authors: David A Cooper; Jayvant Heera; James Goodrich; Margaret Tawadrous; Michael Saag; Edwin Dejesus; Nathan Clumeck; Sharon Walmsley; Naitee Ting; Eoin Coakley; Jacqueline D Reeves; Gustavo Reyes-Teran; Mike Westby; Elna Van Der Ryst; Prudence Ive; Lerato Mohapi; Horacio Mingrone; Andrzej Horban; Frances Hackman; John Sullivan; Howard Mayer Journal: J Infect Dis Date: 2010-03-15 Impact factor: 5.226
Authors: Richard M Dunham; Ivan Vujkovic-Cvijin; Steven A Yukl; Mara J Broadhurst; Pʼng Loke; Rebecca G Albright; Joseph K Wong; Michael M Lederman; Ma Somsouk; Peter W Hunt; Jeffrey N Martin; Steven G Deeks; Joseph M McCune Journal: J Acquir Immune Defic Syndr Date: 2014-02-01 Impact factor: 3.731
Authors: Marie R McCausland; Angélica Cruz-Lebrón; Heather A Pilch-Cooper; Scott Howell; Jeffrey M Albert; Young S Park; Alan D Levine Journal: AIDS Date: 2020-05-01 Impact factor: 4.177
Authors: Allan R Tenorio; Yu Zheng; Ronald J Bosch; Supriya Krishnan; Benigno Rodriguez; Peter W Hunt; Jill Plants; Arjun Seth; Cara C Wilson; Steven G Deeks; Michael M Lederman; Alan L Landay Journal: J Infect Dis Date: 2014-05-01 Impact factor: 5.226
Authors: Nikolas I Wada; Jay H Bream; Otoniel Martínez-Maza; Bernard Macatangay; Shannon R Galvin; Joseph B Margolick; Lisa P Jacobson Journal: Clin Infect Dis Date: 2016-06-25 Impact factor: 9.079
Authors: M N T Kremers; R Janssen; C C H Wielders; L M Kampschreur; P M Schneeberger; P M Netten; A de Klerk; H M Hodemaekers; M H A Hermans; D W Notermans; P C Wever Journal: Clin Vaccine Immunol Date: 2014-01-29
Authors: K M Emanuel; K Runner; Z D Brodnik; B M Morsey; B G Lamberty; H S Johnson; A Acharya; S N Byrareddy; R A España; H S Fox; P J Gaskill Journal: iScience Date: 2022-04-06