Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression

Abstract

The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

Cytokine signals propagate through the brain

“…Centrally delivered IL-1Ra abrogates these effects. 70 Together, these findings suggest that the ventricular IL-1␤ induces via IL-1R and/or AP-1, IL-1␤ and other cytokines' synthesis, a bona fide cytokines cascade. The IL-1␤ signal may also propagate by diffusion of IL-1␤ throughout the CSF.…”

The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

“…This contrasts with LPS-induced anorexia, which is inhibited by IL-1ra (14,23). It is unlikely that the lack of effect of IL-1ra on the poly I:C-induced reduction in food intake is because of loss of activity over time, since we have previously demonstrated that a similar dose of IL-1ra inhibited the effect of the appetite suppressant leptin over a 22-h period (30).…”

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

“…LPS administration stimulates the release of pro-inflammatory cytokines such as IL1, TNFa, IL6, and so on (O'Reilly et al 1988, Plata-Salaman 1999, Wong & Pinkney 2004, Bennani-Baiti & Walsh 2011. These cytokines may be associated with the induction of anorexia; however, hypothalamic inflammatory signals, rather than peripheral, have been identified as the major causes of LPS-induced anorexia (Laye et al 2000, Plata-Salaman 2000, Wisse et al 2007). In line with previous studies, the mRNA levels of cytokines such as IL1a, IL1b, TNFa, and IL6 were significantly increased in the hypothalamus after LPS administration.…”