Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29).
The interferon lambda family (IFN-lambda1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members. These novel cytokines are induced during viral infection and, like type-1 interferons, display significant anti-viral activity. In order to understand their function in more depth, we have examined the ability of IFN-lambda1/IL-29 to regulate cytokine production by human immune cells. Whole peripheral blood mononuclear cells (PBMC) exposed to IFN-lambda1 specifically upregulated IL-6, -8 and -10 but there were no visible effects on TNF or IL-1. This response was produced in a dose-dependant fashion and was inhibited by IL-10. Examination of purified cell populations isolated from PBMC demonstrated that monocytes, rather than lymphocytes, were the major IFN-lambda1-responsive cellular subset, producing IL-6, -8 and -10 in response to IFN-lambda1. Monocyte responses induced by low-level LPS stimulation were also synergistically enhanced by the presence of IFN-lambda1. Human macrophages were also shown to react to IFN-lambda1 similarly to monocytes, by producing the cytokines IL-6, -8 and -10. In conclusion, we have shown that IFN-lambda1, a cytokine produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and may therefore be important in activating innate immune responses at the site of viral infection.
Jordan
W J
WJ
Department of Oral Biology, New Jersey Dental School, Newark, NJ, USA.
Eskdale
J
J
Boniotto
M
M
Rodia
M
M
Kellner
D
D
Gallagher
G
G
D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons; D007378:Interleukins / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014780:Viruses / Q000276:immunology; D000095022:Interferon Lambda
D016207:Cytokines; D007372:Interferons; D007378:Interleukins; D008070:Lipopolysaccharides; C000624353:interferon-lambda, human; D000095022:Interferon Lambda