Role of CINC-1 and CXCR2 receptors on LPS-induced fever in rats.

Yamashiro, Lívia Harumi; de Souza, Glória Emília Petto; de Melo Soares, Denis

Yamashiro, Lívia Harumi; de Souza, Glória Emília Petto; de Melo Soares, Denis.

Afiliação

Yamashiro LH; Laboratory of Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical Science, University of São Paulo, Ribeirão Preto, SP, Brazil.
de Souza GEP; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
de Melo Soares D; Laboratory of Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical Science, University of São Paulo, Ribeirão Preto, SP, Brazil.

Pflugers Arch ; 471(2): 301-311, 2019 02.

Article em En | MEDLINE | ID: mdl-30349936

RESUMO

The classic model of fever induction is based on the administration of lipopolysaccharide (LPS) from Gram-negative bacteria in experimental animals. LPS-induced fever results in the synthesis/release of many mediators that assemble an LPS-fever cascade. We have previously demonstrated that cytokine-induced neutrophil chemoattractant (CINC)-1, a Glu-Leu-Arg (ELR) + chemokine, centrally administered to rats, induces fever and increases prostaglandin E2 in the cerebrospinal fluid. We now attempt to investigate the involvement of CINC-1 and its functional receptor CXCR2 on the fever induced by exogenous and endogenous pyrogens in rats. We also investigated the effect of reparixin, an allosteric inhibitor of CXCR1/CXCR2 receptors, on fever induced by either systemic administration of LPS or intracerebroventricular injection of CINC-1, as well as TNF-α, IL-1ß, IL-6, or ET-1, known mediators of febrile response. Our results show increased CINC-1 mRNA expression in the liver, hypothalamus, CSF, and plasma following LPS injection. Moreover, reparixin administered right before CINC-1 or LPS abolished the fever induced by CINC-1 and significantly reduced the response induced by LPS. In spite of these results, reparixin does not modify the fever induced by IL-1ß, TNF-α, and IL-6, but significantly reduces ET-1-induced fever. Therefore, it is plausible to suggest that CINC-1 might contribute to LPS-induced fever in rats by activating CXCR2 receptor on the CNS. Moreover, it can be hypothesized that CINC-1 is placed upstream TNF-α, IL-1ß, and IL-6 among the prostaglandin-dependent fever-mediator cascade and amidst the prostaglandin-independent synthesis pathway of fever.

Assuntos

Quimiocina CXCL1/metabolismo; Febre/induzido quimicamente; Febre/metabolismo; Lipopolissacarídeos/farmacologia; Receptores de Interleucina-8B/metabolismo; Animais; Líquido Cefalorraquidiano/efeitos dos fármacos; Líquido Cefalorraquidiano/metabolismo; Hipotálamo/efeitos dos fármacos; Hipotálamo/metabolismo; Interleucina-6/metabolismo; Interleucina-8/metabolismo; Fígado/efeitos dos fármacos; Fígado/metabolismo; Macrófagos/efeitos dos fármacos; Macrófagos/metabolismo; Masculino; Prostaglandinas/metabolismo; RNA Mensageiro/metabolismo; Ratos; Ratos Wistar; Linfócitos T/efeitos dos fármacos; Linfócitos T/metabolismo; Fator de Necrose Tumoral alfa/metabolismo

Palavras-chave

CINC-1; CXCR2 receptor; Fever; LPS; Reparixin

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lipopolissacarídeos / Receptores de Interleucina-8B / Quimiocina CXCL1 / Febre Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Pflugers Arch Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha

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