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1.
Eur Cytokine Netw ; 18(2): 49-58, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17594937

ABSTRACT

Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)alpha, IL-1beta, and interferon (IFN)gamma. Since pro-inflammatory cytokines have been implicated in the production of human immunodeficiency virus type 1 (HIV-1), cytokine synthesis in whole blood cultures were determined during a 4-week course of subcutaneous IL-10 injections in 33 HIV-1-infected patients. Patients were randomized into four groups: placebo (nine), IL-10 at 1 microg/kg/day (nine), IL-10 at 4 microg/kg/day (six) and IL-10 at 8 microg/kg three times per week (nine). Whole blood was obtained at the beginning and conclusion of the study and was stimulated for 24 hours with the combination of IL-18 plus lipopolysaccharide. TNFalpha production in stimulated whole blood was reduced three and six hours after the first injection of IL-10 compared to subjects injected with the placebo. After four weeks of treatment, production of IFNgamma was suppressed in a greater number of patients in the IL-10 treatment groups compared to subjects in the placebo group. Similarly, IL-1beta production was lower in the IL-10 treatment groups compared to subjects receiving placebo. In contrast, after four weeks of IL-10, circulating levels of the anti-inflammatory TNF soluble receptor p55 increased dose-dependently compared to placebo subjects. Patient heterogeneity and small sample size presented difficulties in establishing statistical significance. Although the cytokine changes in our study did not demonstrate statistically significant changes, the data nevertheless reveal that four weeks of IL-10 therapy in HIV-1 infected subjects produced the anticipated suppression of pro-inflammatory cytokines.


Subject(s)
Anti-HIV Agents/pharmacology , HIV Infections/drug therapy , Interleukin-10/therapeutic use , Adult , Cytokines/metabolism , Double-Blind Method , Female , Humans , Inflammation , Interferon-gamma/metabolism , Interleukin-1beta/metabolism , Male , Middle Aged , Placebos , Prospective Studies
2.
J Infect Dis ; 195(5): 734-8, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17262717

ABSTRACT

Interleukin (IL)-18 generates T helper 1-type immunity and inhibits human immunodeficiency virus type 1 (HIV-1) in primary cells in vitro. Because IL-18 may participate in HIV-1 containment, whole-blood IL-18 levels were measured in 20 healthy control subjects and longitudinally in 28 subjects with early HIV-1 infection. Compared with those in control subjects, IL-18 levels were higher during early HIV-1 infection, and IL-18 levels predicted reduced CXCR4 HIV-1 coreceptor expression and diminished interferon (IFN)- gamma levels. By contrast, a direct association between IL-18 and IFN- gamma levels was observed in blood stimulated with lipopolysaccharide. During early HIV-1 infection, IL-18 may regulate HIV-1 coreceptor expression and have antiretroviral activity.


Subject(s)
HIV Infections/blood , HIV Infections/metabolism , HIV-1/isolation & purification , Interferon-gamma/metabolism , Interleukin-18/blood , Receptors, CXCR4/metabolism , Adult , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Interleukin-18/metabolism , Male , Middle Aged
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