Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior

Background: interleukin (il)-6 is produced in the brain during peripheral infection and plays an important but poorly understood role in sickness behavior. therefore,this study investigated the capacity of soluble gp130 (sgp130),a natural inhibitor of the il-6 trans-signaling pathway to regulate il-6 production in microglia and neurons in vitro and its effects on lipopolysaccharide (lps)-induced sickness behavior in vivo.methods: a murine microglia (bv.2) and neuronal cell line (neuro.2a) were used to study the effects of stimulating and inhibiting the il-6 signaling pathway in vitro. in vivo,adult (3-6 mo) balb/c mice received an intracerebroventricular (icv) injection of sgp130 followed by an intraperitoneal (i.p.) injection of lps,and sickness behavior and markers of neuroinflammation were measured.results: soluble gp130 attenuated il-6- and lps-stimulated il-6 receptor (il-6r) activation along with il-6 protein release in both microglial (bv.2) and neuronal (neuro.2a) cell types in vitro. moreover,in vivo experiments showed that sgp130 facilitated recovery from lps-induced sickness,and this sgp130-associated recovery was paralleled by reduced il-6 receptor signaling,mrna,and protein levels of il-6 in the hippocampus.conclusions: taken together,the results show that sgp130 may exert an anti-inflammatory effect on microglia and neurons by inhibiting il-6 binding. these data indicate that sgp130 inhibits the lps-induced il-6 trans-signal and show il-6 and its receptor are involved in maintaining sickness behavior. © 2011 burton et al; licensee biomed central ltd.