Central leukotrienes modulate fever tolerance to LPS in rats

Author(s)

Santos, Bruna M. ^[1] ; Costa, Luis H. A. ^[2] ; Rocha, Maria J. ^{[2, 3]} ; Branco, Luiz G. S. ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Neurosci & Behav Sci, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Basic & Oral Biol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Thermal Biology; v. 84, p. 245-249, AUG 2019.
• Web of Science Citations: 0

Abstract

Leukotrienes mediate several inflammatory events such as neutrophil chemoattraction, leukocyte adhesion, and central-release of cytokines and fever. However, there is no information available about their putative role in lipopolysaccharide (LPS) tolerance. The rational of the present study was to find out if central leukotrienes are involved in the development of LPS tolerance. Thus, we inhibited central leukotriene synthesis in tolerant rats using a pharmacological tool, i.e., a selective inhibitor of leukotriene synthesis MK-886 injected into the third ventricle (3V) of rats. Body core temperature (Tb) was measured using a datalogger placed inside the abdominal cavity. A low-dose of LPS (100 mu g/kg ip) was given for 4 consecutive days to induce LPS tolerance. At day 4, rats received a microinjection of MK-886 into the 3V immediately before LPS, whereas control groups were treated with vehicle (saline). We observed that LPS failed to induce plasma cytokines surges, increased hypothalamic PGE(2) levels and fever 3 days post LPS treatment, aptly characterizing the tolerance. When MK-886 was given to control rats treated with saline, no significant change in Tb was observed. However, a full LPS-induced fever was observed in tolerant rats pretreated with MK-886, which was associated with an enhancement in the hypothalamic PGE(2) levels, that were not accompanied by plasma cytokines (IL-1 beta, and IL-6) and PGE(2) surges. These data are consistent with the notion that central leukotrienes play a role in fever tolerance to LPS. (AU)

• FAPESP's process: 16/09364-3 - Role of endogenous preoptic hydrogen sulfide modulating LPS tolerance.
• Grantee: Bruna Maitan Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/17681-9 - Pathophysiological changes during systemic inflammation
• Grantee: Luiz Guilherme de Siqueira Branco
• Support Opportunities: Research Projects - Thematic Grants