The role of IL-1β in stress-induced sensitization of proinflammatory cytokine and corticosterone responses

Abstract

Proinflammatory cytokines often sensitize neuronal, hormonal, and behavioral responses to subsequent challenge. Recently, it was observed that exposure to inescapable tailshock enhances peripheral and central proinflammatory cytokine and corticosterone (CORT) responses to subsequent immune challenge up to 4 days later. Thus, we examined the role of central interleukin-1β (IL-1β) in stress-induced sensitization of proinflammatory cytokine and CORT responses to a subsequent immune challenge. Rats were administered IL-1 receptor antagonist (IL-1ra) or vehicle into the intra-cisterna magna 1 h prior to tailshock (100, 1.6 mA 5 s shocks) exposure. Twenty-four hours later, rats were challenged i.p. with 10 μg/kg lipopolysaccharide (LPS) and killed 1 h later. IL-1ra had no effect on basal proinflammatory cytokines, but completely blocked the stress-induced enhancement in central and pituitary IL-1β and plasma IL-6 release following LPS challenge. IL-1ra had no effect on stress-induced enhancement in CORT responses following LPS challenge. Additional rats were administered i.c.v. hrIL-1β or vehicle and returned to their home cage. Twenty-four hours later, rats were challenged i.p. with either saline or 10 μg/kg LPS and killed 1 h later. Central hrIL-1β administration significantly elevated central IL-1β levels and plasma CORT following LPS challenge compared with vehicle-injected controls. These data demonstrate that elevations in central IL-1β, whether stress-induced or exogenously administered, are sufficient for sensitizing central IL-1β and CORT responses to subsequent immune challenge. However, during times of stress, exogenous central IL-1ra administration only blocked sensitization of subsequent central IL-1β responses, not CORT responses, suggesting other factors during the stress response can sensitize CORT responses.