Endogenous interleukia-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis

To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infecti ons, we studied cerebral listeriosis in IL-10-deficient (IL-10(-/-)) and wi ld-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis, IL-10-/- mice succumbed to pri mary as well as secondary listeriosis, whereas WT mice were significantly p rotected from secondary listeriosis by prior intraperitoneal immunization w ith Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10(-/-) mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages, IL-10(- /-) mice recruited significantly increased numbers of leukocytes, in partic ular granulocytes, to the brain, and the intracerebral cytokine (tumor necr osis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synt hase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory pro tein 1 alpha [MIP-l alpha], and MIP-1 beta) transcription was enhanced comp ared to that in WT mice. Despite this prominent hyperinflammation, the freq uencies of intracerebral L. monocytogenes-specific CD8(+) T cells were redu ced and the intracerebral bacterial load was not reduced in IL-10(-/-) mice compared to WT mice. Following intraperitoneal infection, IL-10(-/-) mice exhibited hepatic hyperinflammation without better bacterial clearance; how ever, in contrast to the mice with cerebral listeriosis, they did not succu mb, illustrating that intrinsic factors of the target organ have a strong i mpact on the course and outcome of the infection.