Interleukin-1β costimulates interferon-γ production by human natural killer cells

Megan A. Cooper, Todd A. Fehniger, Anand Ponnappan, Veela Mehta, Mark D. Wewers, Michael A. Caligiuri

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Natural killer (NK) cells are an early source of immunoregulatory cytokines during the innate immune response to viruses, bacteria, and parasites. NK cells provide requisite IFN-γ to monocytes for the elimination of obligate intracellular pathogens. IL-1β is a pro-inflammatory cytokine produced by monocytes (i.e. a monokine) during the early immune response to infection, but its role in promoting human NK cell IFN-γ production is unknown. The current study examines the ability of the monokine IL-1β, plus IL-12, to costimulate IFN-γ production by resting CD56bright and CD56dim human NK cell subsets. CD56bright NK cells stimulated with IL-1β plus IL-12 produced abundant IFN-γ protein, while little IFN-γ was produced in identical cultures of CD56dim cells. In addition, upon activation with IL-1β, CD56bright NK cells exhibited considerably greater phosphorylation of extracellular signal-regulated kinases p42/44 as compared to CD56dim NK cells. Quantitative PCR analysis showed brisk induction of IFN-γ gene expression following costimulation with IL-1β plus IL-12 in CD56bright NK cells, but intracellular flow cytometry revealed that only a fraction (42±2.3%) of CD56bright NK cells account for this high IFN-γ production. These data suggest that the monokine IL-1β is a potent costimulus of IFN-γ production by a subset of NK cells following infectious insult.

Original languageEnglish
Pages (from-to)792-801
Number of pages10
JournalEuropean Journal of Immunology
Issue number3
StatePublished - 2001


  • Human
  • IFN-γ
  • IL-1β
  • Innate immunity
  • NK cell


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