6). Data are shown as mean ± SEM. ANOVA parametric test with Bonferroni correction was used for multiple comparisons. For non-parametric data, we performed Mann–Whitney test. Statistical significance was set at p < 0.05. The authors declare that they have no competing interests. This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

(CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa Selleck Selumetinib do Estado de Minas Gerais (Fapemig), Brazil. ”
“The febrile response is a key phenomenon of the acute phase reaction, which is also characterized by changes in several physiological parameters such as the levels of liver proteins, hormones and cells in blood, sleep phases, food intake, and others (Zeisberger, 1999). Due to the

increased body temperature, defense mechanisms are stimulated, making the febrile response relevant to protection Smad2 phosphorylation of the body’s integrity against invading organisms (Blatteis and Sehic, 1998). The main brain area involved in the control of the body temperature is the anterior hypothalamic pre-optic area (POA), which transduces the information received to a neuronal signal that changes the temperature set point, resulting in fever (Blatteis and Sehic, 1998 and Zeisberger, 1999). The systemic administration of LPS to experimental animals represents one of the classical models of fever induction since it reproduces what naturally occurs during inflammatory and infectious processes. LPS stimulates macrophages, monocytes, and other cells to release cytokines, which can act as endogenous pyrogens to promote fever (Roth and De Souza, 2001). Interleukin (IL)-1β was the first-described endogenous

pyrogen (Dinarello, 1984) and despite the subsequent identification of others it probably remains the most studied Etomidate (Helle et al., 1988, Watanabe, 1992 and Zampronio et al., 1994). A number of mechanisms have been suggested to explain how the peripherally produced endogenous pyrogens exert their effects on the central nervous system (CNS) to produce fever (Banks et al., 1991, Banks et al., 1994, Cao et al., 1996 and Konsman et al., 2004), but it is clear that the synthesis and release of central mediators is required to bring about the necessary changes in the hypothalamic set point. Several central mediators have been proposed including prostaglandins E2 (PGE2) and F2α (PGF2α) (Coelho et al., 1993 and Milton, 1989), corticotrophin releasing factor (CRF) (Rothwell, 1989 and Zampronio et al., 2000), endothelin-1 (ET-1) (Fabricio et al., 1998), endogenous opioids (Benamar et al., 2000 and Fraga et al., 2008), endocannabinoids (Fraga et al., 2009) and also substance P (SP) (Blatteis et al., 1994). Among these, prostaglandins derived from both peripheral and central sources appear to be important (Ivanov et al., 2003 and Steiner et al., 2006).