IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis

Mittal R., et al. The Journal of Experimental Medicine 207(6):1307-192 (2010)

Speaker: Chih-Cheng Kang (康智程)                                     Time: 13:10~14:00,Feb 23, 2011

Commentator: Dr. Chiou-Feng Lin (林秋峰 老師)                Place: Room 601

Abstract:

Escherichia coli K1 is the most common cause of meningitis in premature infants and neonates. The emergence of antibiotic-resistant strains increases the mortality and morbidity rates in newborns. Therefore, it is necessary and urgent to find an alternative therapeutic strategy. The clinical observation found that neonates have a severe inflammatory response, an imbalanced immune homeostatsis, during sepsis. The anti-inflammatory response, which is primarily mediated by IL-10 and TGFβ, is not clear in E. coli infection. Therefore, the authors investigated the role of IL-10 by a newborn IL-10 knockout mouse model of E. coli K1 infection. They demonstrated IL-10-deficiency increased proinflammatory cytokines production, pathogen load and severity disease of meningitis. Administration of exogenous rh-IL-10 had a significant decreased both antibiotic-sensitive and -resistant E. coli from blood of infected mice and showed normal morphology of the brain similar to uninfected mice. The treatment with rh-IL-10 but not antibiotic prevented dilation of ventricles and loss of neurons by micro-CT. On the other hand, IL-10, but not antibiotic or anti-TNF antibody treatment elevated the phagocytosis of E. coli in neutrophils by up-regulation of CR3 expression. The protective effect of IL-10 was abrogated in CR3 knockdown mice and in neutrophils by CR3 siRNA. Furthermore, the level of prostaglandin E-2 (PGE-2), which involved in down-regulation of CR3 expression, was decreased after rh-IL-10 treatment. Thus, this study demonstrate a novel function of IL‑10 in clearance of E. coli K1 via elevating CR3 expression in neutrophils and down-regulation of PGE-2 during the development of E. coli K1 meningitis in neonates and provide a new therapeutic strategy to manipulate E. coli K1 meningitis.

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