Central fractalkine stimulates central prostaglandin E-2 production and induces systemic inflammatory responses

Author(s)

Mota, Clarissa M. D. ^[1] ; Antunes-Rodrigues, Jose ^[1] ; Branco, Luiz G. S. ^{[2, 1]}

Affiliation

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

^[2] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Brain Research Bulletin; v. 140, p. 311-317, JUN 2018.
• Web of Science Citations: 0

Abstract

Fractalkine (FKN; CX3CL1) belongs to gamma-chemokine family and binds to CX3CR1 receptors. Currently, the mechanisms involving FKN-induced inflammatory mediators are research targets in an attempt to study immune diseases mechanisms. Besides, FKN seems to modulate inflammation in the nervous system by inducing the secretion of pro-inflammatory mediators such as prostaglandin E-2 (PGE(2)). PGE(2) is a classic and important mediator of fever that activates warm-responsive neurons in the anteroventral preoptic region of the hypothalamus (AVPO). Here, we tested the hypothesis that central FKN modulates febrigenic signaling both centrally and peripherally. We performed intracerebroventricular (icv) microinjections of saline (1 mu L) or FKN (doses of 5, 50, 500 pg/mu L) in rats and measured body temperature (Tb) besides assessing tail skin temperature (Tsk) as a thermoeffector indicator used to calculate the heat loss index (HLI). We also measured the time course changes in AVPO PGE(2), besides plasma corticosterone (CORT) and interleukin-6 (IL-6) levels. FKN induced a long lasting febrile response in which the highest dose (500 pg/mu L) induced a marked rise on Tb that was accompanied by a reduced Tsk and HLI, consequently. FKN increased AVPO PGE(2) production in a time-dependent manner besides increasing plasma CORT and IL-6 levels. Our data consistently indicate that FKN increases AVPO PGE(2) production and Tb, accompanied by raised plasma IL-6 levels and activation of the hypothalamus-pituitary-adrenal axis. (AU)

• FAPESP's process: 17/01633-8 - Role of serotonin in the preoptic area in the modulation of body temperature and nociception during systemic inflammation
• Grantee: Clarissa Maria Dias Mota
• 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