Reactivity pattern of vasopressin-containing neurons and its relation to the antipyretic reaction in the pregnant guinea pig

Merker, G; Blähser, S; Zeisberger, Eugen

doi:10.1007/bf00234032

Cited by 68 publications

(22 citation statements)

References 16 publications

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“…A likely candidate was AVP, for which there is persuasive evidence that it acts as an endogenous antipyretic (39). Initial evidence in support of AVP acting to suppress fever at term came from the observation that there is increased immunoreactivity for AVP in the hypothalamus during pregnancy in guinea pigs (27) and in push-pull perfusates of the preoptic area in rats (19). However, as evidence in rats to support a role for AVP as an endogenous antipyretic responsible for the suppression of fever at parturition has been largely negative (7, 10), we turned our attention to a possible alteration in the cascade of events leading to fever.…”

Section: Discussionmentioning

confidence: 99%

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Mouihate¹,

Ms²,

Nakamura

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus. Am J Physiol Regul Integr Comp Physiol 283: R800-R805, 2002; 10.1152/ ajpregu.00258.2002The fever response is blunted at near term. As the enzyme cyclooxygenase-2 (COX-2) plays a critical role in fever development, we measured its expression in rat hypothalamus during pregnancy and lactation. Western blot analysis revealed a 72-kDa COX-2-immunoreactive band in non-immune-challenged, pregnant rats at day 15 of pregnancy. In contrast, it was almost undetectable at near term and at lactation day 5. COX-2 was significantly induced at the 15th day of pregnancy and at the 5th lactating day after intraperitoneal lipopolysaccharide (50 g/kg). However, this COX-2 induction was significantly reduced at near term compared with values before and after term. The protein levels of the EP3 receptor in the hypothalamus, one of the prostaglandin E 2 (PGE2) receptors suggested to be a key receptor for fever induction, were unaffected throughout the pregnancy and lactation in both non-immune-challenged and lipopolysaccharide-treated rats. These data suggest that suppression of fever at near term is associated with a significantly reduced induction of COX-2 by lipopolysaccharide, resulting in a reduced production of PGE 2. Altered expression of the EP3 receptor does not seem to be involved in this fever refractoriness at near term.cyclooxygenase-2; parturition; lipopolysaccharide; prostaglandin receptor; EP3 receptor FEVER, A MAJOR PART of host defense, is thought to be of beneficial and adaptive value (15). Thus the inability to develop a fever response to pathogens can be detrimental (16). An absent or reduced fever has been observed in pregnant animals at near term (14) and, in some circumstances, is associated with abortion or mortality (23). This febrile refractoriness has been observed in many species, including guinea pig (55), rabbits (28), sheep (14), and rats (7,23,24), and has been observed in response to both peripherally injected pyrogens (14, 23, 55) and, to a lesser extent, to centrally infused prostaglandins (7,24,48). The fact that fever suppression is most dramatic in response to systemically administered LPS suggests that several steps in the cascade of responses to peripherally injected LPS may be affected.In response to bacterial pyrogens such as LPS, immunocompetent cells generate endogenous cytokines, which signal to the central nervous system through either humoral or neuronal pathways (for review, see Ref. 8) to induce expression of cyclooxygenase-2 (COX-2) (6, 22). The activity of this enzyme results in the cyclooxygenation of arachidonic acid and subsequently the production of PGE 2 , which acts largely in the anterior hypothalamus/preoptic area (47). COX-2 is present in basal conditions in the brain (3, 41), but in inflammation, it is induced specifically in the endothelium of brain capillaries (18,25). Levels of COX-2 have been correlated to levels of PGE 2 during LPS-induced fever (54). Because...

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Section: Discussionmentioning

confidence: 99%

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Mouihate¹,

Ms²,

Nakamura

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Vasopressin-ir projections of the BNST and MeA also exhibit reproduction-related changes in females. For example, vasopressin-ir fibers in the lateral septum are more intensely stained in pregnant than in nonpregnant guinea pigs (Merker et al 1980). In addition, the lateral habenular nucleus contains higher levels of assayable vasopressin in lactating than in pregnant rats (Caldwell et al 1987), and the release of vasopressin from the septum is markedly higher in pregnant and parturient, than in sexually naive, female rats (Landgraf et al 1991).…”

Section: Orchestration Of Steroid-responsive Functionsmentioning

confidence: 99%

Studying neurotransmitter systems to understand the development and function of sex differences in the brain: the case of vasopressin

Vries¹,

Geert²

1995

Neurobiological Effects of Sex Steroid Hormones

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“…Furthermore, we demonstrated that neutralization of endogenous IL-1ra in vivo, using a specific antiserum, results in significantly higher fever responses to LPS in rats (12). The ability of IL-1ra to limit the pyrogenic effects of endogenous IL-1 during infection may be especially important in situations where increases in body temperature could be particularly detrimental, such as to the developing fetus during gestation (4,18,30,42).It is now well documented that febrile responses to infectious agents are significantly attenuated in several mammalian species near term of pregnancy (14,19,25,41,43,69). Although it is tempting to speculate that this may in part be due to the actions of endogenous IL-1ra, little evidence exists to support this to date.…”

mentioning

confidence: 99%

“…It is now well documented that febrile responses to infectious agents are significantly attenuated in several mammalian species near term of pregnancy (14,19,25,41,43,69). Although it is tempting to speculate that this may in part be due to the actions of endogenous IL-1ra, little evidence exists to support this to date.…”

mentioning

confidence: 99%

Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats

Ashdown¹,

Poole²,

Boksa³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Ashdown H, Poole S, Boksa P, Luheshi GN. Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats. Am J Physiol Regul Integr Comp Physiol 292: R1667-R1674, 2007. First published November 30, 2006; doi:10.1152/ajpregu.00274.2006.-Febrile responses to bacterial pathogens are attenuated near term of pregnancy in several mammalian species. It is unknown, however, whether this reflects a fundamental physiological adaptation of female rats or whether it is specific to pregnancy. The aims of this study therefore were 1) to determine whether febrile responses to the bacterial endotoxin lipopolysaccharide (LPS) are attenuated in female vs. male rats and, if so, to identify possible mechanisms involved in modulating this and 2) to assess whether plasma concentrations of the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), an important regulator of fever, are dependent on the physiological state of the female and could therefore be involved in modulating febrile responses. We found febrile responses were attenuated in cycling female vs. male rats and also in near-term pregnant dams vs. cycling females after intraperitoneal injection of LPS (0.05 mg/kg). Plasma levels of IL-1ra were significantly greater in female rats after injection of LPS, particularly during pregnancy, than in males. This was accompanied by attenuated levels of hypothalamic IL-1␤ and cyclooxygenase-2 mRNA, two key mediators of the febrile response, in female rats. Furthermore, increasing plasma levels of IL-1ra in male rats by intraperitoneal administration of the recombinant antagonist attenuated hypothalamic mRNA levels of these mediators after LPS. These data suggest that there is a fundamental difference in febrile response to LPS between the genders that is likely regulated by IL-1ra. This may be an important mechanism that protects the developing fetus from potentially deleterious consequences of maternal fever during pregnancy.fever; pregnancy; cyclooxygenase-2; interleukin-1␤; cytokines FEVER IS A COMPLEX PHYSIOLOGICAL response mounted by the host to facilitate the resolution of infection after exposure to invading viral or bacterial pathogens. This central nervous systemorchestrated response involves the production and action of prostaglandins (PGE 2 ) on hypothalamic thermosensitive neurons, a process that is initiated through the action of systemic pyrogenic mediators of the cytokine family (16, 59). These key inflammatory proteins are readily induced after exposure to exogenous pyrogens, such as the bacterial product lipopolysaccharide (LPS), and increase in the periphery to reflect the rise in body temperature (16, 51). The proinflammatory cytokine IL-1␤ is a major peripheral mediator of LPS-induced fever, which is known to trigger increases in body temperature via cyclooxygenase-2 (COX-2)-dependent production of PGE 2 in the brain (35). Studies in experimental animals have demonstrated that recombinant IL-1␤, administered either systemically or dir...

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Reactivity pattern of vasopressin-containing neurons and its relation to the antipyretic reaction in the pregnant guinea pig

Cited by 68 publications

References 16 publications

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Studying neurotransmitter systems to understand the development and function of sex differences in the brain: the case of vasopressin

Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats

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