Raised serum levels of interleukin-18 is associated with disease progression and may contribute to virological treatment failure in HIV-1-infected patients.
To gain further insight into the possible role of interleukin (IL)-18 in HIV-1 infection we examined serum levels of IL-18 in various clinical and immunological stages of HIV-1 infection during cross-sectional (n = 41) and longitudinal testing (n = 20) and during HAART (n = 21, 24 months follow-up). Our main findings were that HIV-1-infected patients had significantly raised IL-18 levels comparing healthy controls, particularly in those with advanced disease, that while HAART induced a marked decline in IL-18, virological treatment failure was associated with persistently raised IL-18 levels during such therapy and that our in vitro experiments showed an IL-18-mediated up-regulation of the HIV-1 coreceptor CXCR4 and the pro-apoptotic mediator TRAIL in PBMC from HIV-1-infected patients receiving HAART. HIV-1 infection appears to be characterized by persistently raised IL-18 levels and during HAART, such a pattern was associated with virological treatment failure, possibly contributing to immunodeficiency and HIV-1 replication in these patients.
Stylianou
E
E
Section of Clinical Immunology and Infectious Diseases, Rikshospitalet University Hospital, Oslo, Norway.
Bjerkeli
V
V
Yndestad
A
A
Heggelund
L
L
Waehre
T
T
Damås
J K
JK
Aukrust
P
P
Frøland
S S
SS
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003430:Cross-Sectional Studies; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D020382:Interleukin-18 / Q000097:blood* / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D017211:Treatment Failure
D018925:Chemokines; D020382:Interleukin-18; D012333:RNA, Messenger; D019707:Receptors, Chemokine