Inhibition of the constitutive and induced IFN-beta production by IL-4 and IL-10 in murine peritoneal macrophages.
We had previously reported that freshly harvested peritoneal macrophages (PM) are in a type I IFN-mediated antiviral state, which is lost during in vitro culture of PM, concomitantly with a progressive decline in the expression of IFN-beta. We report herein that in vitro culture of PM in the presence of IL-4 or IL-10 results in an enhanced decay of the IFN-beta-mediated antiviral state to vesicular stomatitis virus (VSV). Moreover, IL-4 and IL-10 inhibited the production of type I IFN induced by LPS or NDV infection, as assessed by IFN production and induction of IFN-mediated antiviral state. The accumulation and physiological turnover of IFN-beta mRNA was not affected by IL-4 or IL-10. Finally, neither IL-10 nor IL-4 exerted any inhibitory effect on the antiviral activity induced by exogenous type-I IFN. These results suggest that Th2 cytokines, such as IL-4 and IL-10, act as negative regulators of the type I IFN-mediated antiviral response in PM and may represent stop signals for the constitutive or induced type I IFN expression in PM.
Varano
B
B
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Fantuzzi
L
L
Puddu
P
P
Borghi
P
P
Belardelli
F
F
Gessani
S
S
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009522:Newcastle disease virus; D012333:RNA, Messenger / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D016899:Interferon-beta