Central leukotrienes modulate fever tolerance to LPS in rats
| Autor: | Luiz G.S. Branco, Maria José Alves da Rocha, Bruna M. Santos, Luís Henrique Angenendt da Costa |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Leukotriene synthesis Lipopolysaccharides Male Leukotrienes Lipopolysaccharide Fever Physiology 030310 physiology medicine.medical_treatment Hypothalamus Pharmacology 010603 evolutionary biology 01 natural sciences Biochemistry Dinoprostone Body Temperature 03 medical and health sciences chemistry.chemical_compound Medicine Animals Rats Wistar Body core temperature Microinjection Saline 0303 health sciences business.industry chemistry lipids (amino acids peptides and proteins) General Agricultural and Biological Sciences business Developmental Biology |
| Zdroj: | Journal of thermal biology. 84 |
| ISSN: | 0306-4565 |
| Popis: | 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 μg/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 PGE2 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 PGE2 levels, that were not accompanied by plasma cytokines (IL-1β, and IL-6) and PGE2 surges. These data are consistent with the notion that central leukotrienes play a role in fever tolerance to LPS. |
| Databáze: | OpenAIRE |
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