title: Attenuated fever in rats during late pregnancy is linked to suppressed interleukin-6 production after localized inflammation with turpentine.
abstract: An attenuated fever response to pathogens during late pregnancy is a phenomenon that has been described in several mammalian species, and although mechanisms are not completely understood, decreased prostaglandin E2 (PGE2) synthesis has been implicated. Upstream of PGE2, there is evidence to suggest that anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1ra) could play a significant role. In the present study we addressed the role of pro-inflammatory cytokines during late pregnancy, specifically interleukin-6 (IL-6), an important circulating mediator in fever. Turpentine oil (TURP), a very potent pyrogen and activator of IL-6, was injected into the hind-limb muscle of rats at the 18th day of pregnancy (GD 18) or in non-pregnant (NP) age-matched female controls. As expected, TURP injection induced a highly significant fever in the NP animals, which peaked 11 h post-injection and lasted for over 24 h. This was accompanied by a significant rise in circulating IL-6 levels, which correlated with changes in PGE2 synthesizing enzymes expression in the hypothalamus. In complete contrast, TURP-induced fever was totally absent in GD 18 animals whose body temperature did not deviate from basal values. The lack of response was additionally reflected by the absence of change in IL-6 concentration and by the significant attenuation of PGE2 synthesizing enzymes expression, which correlated with the suppressed expression of SOCS3, a hypothalamic marker of IL-6 activity. Contrary to the changes in circulating IL-6 levels at GD 18, IL-1ra was induced to levels comparable to those of NP females, suggesting that the influence of this anti-inflammatory cytokine on the fever response to TURP is at best minimal. These data further confirm the importance of IL-6 in fever generation and provide evidence that it may be a key component of the attenuated fever response in late pregnancy.
authors.affiliation: Douglas Hospital Research Centre, Department of Psychiatry, McGill University, 6875 LaSalle Boulevard, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Argel
authors.initials: A
authors.lastname: Aguilar-Valles
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Mistry
authors.forename: Sylvain
authors.initials: S
authors.lastname: Williams
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005334:Fever / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007509:Irritants; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000502:physiology*; D011749:Pyrogens / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014425:Turpentine
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D007509:Irritants; D011749:Pyrogens; D012333:RNA, Messenger; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015232:Dinoprostone; D014425:Turpentine