Different modes of IL-10 and TGF-beta to inhibit cytokine-dependent IFN-gamma production: consequences for reversal of lipopolysaccharide desensitization.
J Immunol
; 170(10): 5260-7, 2003 May 15.
Article
em En
| MEDLINE
| ID: mdl-12734375
ABSTRACT
LPS hyporesponsiveness is characterized by a diminished production of proinflammatory cytokines which can be caused by pretreatment with either LPS (=LPS desensitization) or the combination of the anti-inflammatory cytokines IL-10 and TGF-beta. However, the resulting hyporesponsive states differ regarding their reversibility by the IFN-gamma-inducing cytokine IL-12. Therefore, we aimed at studying the reasons for this differential IL-12 responsiveness of IFN-gamma-producing cells and its consequences for LPS hyporesponsiveness in more detail. In an in vitro IL-12/IL-18 responsiveness model, we demonstrated that IL-10, if permanently present, does not directly inhibit IL-12/IL-18 responsiveness in T/NK cells but indirectly interferes with IFN-gamma production in the presence of monocytes. In contrast, TGF-beta acted directly on IFN-gamma-producing cells by interfering with IL-12/IL-18 responsiveness. After removal of IL-10 but not of TGF-beta, LPS hyporesponsiveness can be reverted by IL-12/IL-18. Consequently, the addition of recombinant TGF-beta during LPS desensitization rendered PBMCs hyporesponsive to a reversal by IL-12/IL-18. Our data suggest that the persistence of IL-10 and the presence of TGF-beta determine the level of IFN-gamma inhibition and may result in different functional phenotypes of LPS desensitization and LPS hyporesponsiveness in vitro and in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
/
Fator de Crescimento Transformador beta
/
Dessensibilização Imunológica
/
Interferon gama
/
Interleucina-10
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Alemanha