Mechanisms of action of intravenous immunoglobulin in septic encephalopathy

Abstract

Acute brain dysfunction associated with sepsis is a serious complication that results in morbidity and mortality. Intravenous immunoglobulin (IVIg) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Our results suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might suppress classical complement pathway by reducing C5a activity and proapoptotic NF-kappa B and Bax expressions, thereby, inhibiting major inflammation and apoptosis cascades. Future animal model experiments performed with specific C5aR and NF-kappa B agonists/antagonists or C5aR-deficient mice might more robustly disclose the significance of these pathways. C5a, C5aR, and NF-kappa B, which were shown to be the key molecules in brain injury pathogenesis in sepsis, might also be utilized as potential targets for future treatment trials of septic encephalopathy.