Effect of a four-week course of interleukin-10 on cytokine production in a placebo-controlled study of HIV-1-infected subjects

Gregory B. Pott, Carrie A. Sailer, Reuven Porat, Robert L. Peskind, Amy C. Fuchs, Jonathan B. Angel, Paul R. Skolnik, Mark A. Jacobson, Michael F. Giordano, Alexandre LeBeaut, Paul C. Grint, Charles A. Dinarello, Leland Shapiro

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)α, IL-1β, and interferon (IFN)γ. 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 μg/kg/day (nine), IL-10 at 4 μg/kg/day (six) and IL-10 at 8 μg/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. TNFα 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 IFNγ was suppressed in a greater number of patients in the IL-10 treatment groups compared to subjects in the placebo group. Similarly, IL-1β 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 proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalEuropean cytokine network
Volume18
Issue number2
DOIs
StatePublished - Jun 2007

Keywords

  • Ex vivo
  • HIV-1
  • Interleukin-10
  • Pro-inflammatory cytokines
  • Whole blood

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry

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