NIK1.1 cells downregulate murine endotoxin-induced uveitis following intraocular administration of interleukin-12

• Autor(a) principal: Figueiredo, F.
• Data de Publicação: 2007
• Outros Autores: Commodaro, Alessandra Gonçalves [UNIFESP], Camargo, M. M. de, Rizzo, L. V., Belfort, Rubens Junior [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1111/j.1365-3083.2007.01988.x; http://repositorio.unifesp.br/handle/11600/29883

To evaluate the role of IFN-gamma (interferon gamma) in IL-12- (interleukin12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-gamma-deficient (GKO) ium endotoxin as a model mice were injected with 250 pg of Salmonella typhymurium for EIU. Animals were then injected intraocularly with 100 ng of rIL-12 or the equivalent volume of Phosphate-buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase-polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN-gamma was performed using the R4-6A2 antibody. C57BL/6 mice treated with rIL-12 intraocularly were protected from the development of EIU. Neutralization of IFN-gamma with a monoclonal antibody abrogated such protection. the IL-12 protective effects were lost in NK1.1-depleted mice. Intraocular IL-12 decreased the expression of keratinocyte-derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP-2) gene. the protective effect of IL-12 during EIU occurs through production of IFN-gamma by NKLI+ cells. IL-12-induced higher levels of IFN-gamma are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.