Anti-Inflammatory Activity of IVIG Protects Against HSV Encephalitis. (45.26)

Abstract

Abstract Susceptible mouse strains like 129 mice develop HSV encephalitis (HSE) characterized by large focal inflammatory CNS lesions associated with massive accumulation of monocytes and neutrophils, resulting in rapid onset of death. In contrast, regulated CNS inflammatory responses protect resistant C57BL/6 mice against HSE. Disease progression was not affected by early inhibition of HSV replication consistent with immune mediated pathology and not virus cytopathology, causing death. Intravenous immunoglobulin (IVIG) possesses potent anti-inflammatory activities and is highly effective in treating various inflammatory diseases. We report here that IVIG protects against fatal HSE by inhibiting CNS inflammation through a mechanism(s) independent of HSV antibody. Both sialylated and non-sialylated but not deglycosylated IgGs mediated protection. IVIG treatment profoundly altered host immune responses, promoting lymphocytic rather than monocytic infiltration of the CNS accompanied by phenotypic alteration of macrophages and a dramatic expansion of CD4+ Tregs that accumulated in peripheral lymphoid organs. However the Tregs were not solely responsible for inhibiting inflammation. IL-10 secreted by APCs was primarily responsible for suppressing CNS inflammation. Despite controlling virus replication IVIG treated IL-10 deficient mice were unable to control CNS inflammation and succumbed eventually. In addition, FcγR2b was critical for IVIG’s immunomodulatory activity.