IFN-beta and TGF-beta differentially regulate IL-12 activity in human peripheral blood mononuclear cells.
Both IFN-beta and TGF-beta have demonstrated their ability to antagonize several of the stimulatory activities of IFN-gamma on human macrophages, thereby classifying them as Th2-like. Aiming at a further characterization of their role in Th1/Th2 development, we studied their possible interaction with IL-12, the key Th1 cytokine. We found that IFN-beta by itself induced modest amounts of IFN-gamma, but was able to synergize with IL-12 for IFN-gamma induction. TGF-beta, on the other hand, had no effect by itself and inhibited significantly the IL-12-induced IFN-gamma secretion. The differential effect of IFN-beta and TGF-b on IL-12 bioactivity was most pronounced upon IFN-gamma synthesis, since IFN-beta induced only marginal amounts of IL-10 and IL-12 and TGF-beta diminished constitutive IL-10 production, while neither had a significant effect on TNF-alpha production. Although monocytes did not produce detectable IFN-gamma with any of the stimuli, adherent cells were found to cooperate with non-adherent lymphocytes for maximal IFN-gamma production. However, IL-18, a monocyte-derived IFN-gamma-inducing cytokine able to synergize with IL-12, was undetectable in IFN-beta or IFN-beta+IL-12-stimulated cells. In conclusion, the ability of IFN-beta to synergize with IL-12 for IFN-gamma synthesis, without significant concomitant IL-10 production, suggest a strong boost to Th1 development, which seems to be IL-18-independent.
Van Weyenbergh
J
J
Laboratório de Imuno-regulação e Microbiologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, 40295-001 Salvador, Bahia, Brazil. ejomaflo@svn.com.br
P Silva
M P
MP
Báfica
A
A
Cardoso
S
S
Wietzerbin
J
J
Barral-Netto
M
M
D002448:Cell Adhesion; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D011994:Recombinant Proteins; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007370:Interferon Type I; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma