Treatment with IL-10 Cures Meningitis in Mouse Model

coli K1 can cause meningitis with the possibility of permanent neurological damage or death. As the bacteria become progressively more resistant to antibiotic treatment, the more powerful antibiotics now in use may cause severe side effects.

In the current study, investigators at the University of Southern California (Los Angeles, USA) tried a new approach to cure E. coli K1 meningitis based on treatment with the naturally occurring cytokine IL-10. IL10 is an anti-inflammatory cytokine encoded by the IL-10 gene. This cytokine is produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has a wide range of effects in immunoregulation and inflammation. It downregulates the expression of Th1 (T-helper cell) cytokines, MHC (major histocompatibility complex) class II antigens, and costimulatory molecules on macrophages. It also enhances B-cell survival, proliferation, and antibody production.

Results published in the May 24, 2010, online edition of the Journal of Experimental Medicine revealed that administration of IL-10 - but not antibiotic or anti-TNF (tumor necrotic factor) antibody treatment- prevented brain damage caused by E. coli. The treatment stimulated elevated expression of complement receptor CR3 in neutrophils and macrophages of infected mice, whereas infected untreated mice displayed increased expression of Fc receptors and Toll-like receptors.

Neutrophils or macrophages pretreated with IL-10 while outside the body exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type mice or mice that lacked the gene for IL-10. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages of mice with E. coli infection.

Since IL-10 is already being used for treatment of adults with certain types of autoimmune disease, the investigators suggested that the potential for its use in treating infants with E.coli K1 infections should be evaluated.

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