HIV-1 is not a major driver of increased plasma IL-6 levels in chronic HIV-1 disease.
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.


METHODS
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.
Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Carey L
CL
Shive
Angélique
A
Biancotto
Nicholas T
NT
Funderburg
Heather A
HA
Pilch-Cooper
Hernan
H
Valdez
Leonid
L
Margolis
Scott F
SF
Sieg
Grace A
GA
McComsey
Benigno
B
Rodriguez
Michael M
MM
Lederman
D000328:Adult; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D015850:Interleukin-6; D012367:RNA, Viral