Central Fractalkine Induces Systemic Inflammation Independently of Hypothalamic Prostaglandin E2

• Published in: The FASEB journal Vol. 32; no. S1; p. 735.2
• Main Authors: Mota, Clarissa Maria Dias, Rocha, Maria José Alves, Antunes‐Rodrigues, José, Siqueira Branco, Luiz Guilherme
• Format: Journal Article
• Language: English
• Published: The Federation of American Societies for Experimental Biology 01-04-2018
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2018.32.1_supplement.735.2

Fractalkine (FKN; CX3CL1) belongs to the 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 E2 (PGE2). PGE2 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. Thus, male Wistar rats (280–350 g, n=5/group) were obtained from the Central Animal Facility at the University of São Paulo in Ribeirão Preto and all the experiments were performed according to the Brazilian society of laboratory animals science and in conformance with the FASEB Statement of Principles for the use of animals in research and education. We performed intracerebroventricular (icv) microinjections of saline (1 μL) and FKN (doses of 5, 50, 500 pg/μL) and measured body temperature (Tb), besides assessing tail skin temperature (Tsk) as a thermoeffector indicator. We also measured AVPO PGE2, plasma corticosterone (CORT) and interleukin‐6 (IL‐6) levels. FKN induced a long lasting febrile response in which the highest dose (500 pg/μL) induced a marked rise on Tb that was accompanied by a reduced Tsk. FKN had no effect on AVPO PGE2 production, whereas caused increases in plasma CORT and IL‐6 levels. Our data consistently indicate that FKN induces fever (reducing Tsk) in a PGE2 independent way probably by increasing plasma IL‐6 levels.
Support or Funding Information
The São Paulo Research Foundation (FAPESP) grant numbers #16/17681‐9 and #17/01633‐8 and the National Council for Scientific and Technological Development (CNPq), Brazil.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.