Interleukin-18: a proinflammatory cytokine in HIV-1 infection.
Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against viruses and intracellular pathogens. Increased levels of circulating IL-18 from HIV-1 infected patients have been reported especially in the advanced and late stages of the disease, whereas in the initial stage serum levels of IL-18 were not increased. In contrast, low production of Il-18 was observed in vitro from peripheral blood mononuclear cells (PBMC) of HIV-1 infected patients, and these results were also observed in macaques infected with simian immunodeficiency virus (SIV). In addition, decreased IL-18 production from PBMC was significantly correlated with low production of IL-2. Furthermore, serum levels of IL-18 significantly decreased after highly active antiretroviral therapy. During the early stage of HIV-1 infection there is a decreased production of gamma interferon (IFN), IL-12 and IL-2 as well as not activation of IL-18 production and this leads to inhibition of Th1 immune response, whereas in the advanced stage of the disease, strong activation of IL-18 production along with persistent decreased production of gamma IFN, IL-12 and IL-2 may promote a Th2 immune response, which leads to persistent viral replication. Several studies have shown increased levels of IL-18 in HIV-seronegative subjects with obesity, insulin resistance and type II diabetes. Metabolic disorders, fat redistribution and cardiovascular manifestations are becoming more frequent in HIV-1 infected patients treated with antiretroviral drugs. Consequently, involvement of IL-18 in these disorders has been postulated and demonstrated in patients with lipodistrophy, or with hypertriglyceridemia. Finally, higher serum levels of IL-18 may represent an useful marker in HIV-1 infected patients with metabolic disorders and fat redistribution, as well as a sensitive predictor of cardiovascular complications in treated patients.
Torre
Donato
D
Section of Infectious Diseases, General Hospital Cittiglio (Varese), Amedeo di Savoia Hospital, University of Turin, Turin, Italy. donatotorre@libero.it
Pugliese
Agostino
A
D000818:Animals; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma