Direct effects of secretory products of immune cells on neurons and glia

Abstract

This review summarizes recent research contributions by Dr. Robert Lisak in collaboration with Dr. Joyce Benjamins on direct effects of secretory products of immune cells on neurons and glia. Highlights from studies analyzing cytokine-induced changes in early gene expression in mixed CNS glial cultures focus on comparison of potential damaging effects of pro-inflammatory cytokines versus protective effects of downregulatory cytokines. The three categories of changes examined include (a) immune-related molecules, (b) neurotrophins, growth factors and structural proteins, and (c) molecules associated with metabolism, signaling and regulation. Subsequent studies in CNS neuronal cultures showed that early responses of neurons to cytokines were fewer in number and lower in magnitude than in glia, consistent with the idea that microglia and astroglia serve as "first responders" to inflammatory signals. To explore the hypothesis that B cells of patients with multiple sclerosis secrete soluble products damaging to oligodendroglia (OL), in collaboration with Dr. Bar-Or at Montreal Neurologic Institute, we compared secretory products of cultured B cells from relapsing remitting multiple sclerosis (RRMS) patients and healthy controls. In support of the hypothesis, 7 supernatants from RRMS B cells induced death of rat OL in vitro, while 3 of 4 control samples did not.

Keywords: B cells; Cytokines; FAT10; Glia; IL-6 signal transducer; Multiple sclerosis; Neuroimmunology; Neurons.