Cyclo‐oxygenase mediation of endotoxin‐induced fever, anterior and posterior pituitary hormone release, and hypothalamic c‐Fos expression in the prepubertal pig

Parrott, R.F.; Vellucci, Sandra V.; Goode, J. A.; Lloyd, D. M.; Forsling, ML

doi:10.1113/expphysiol.1995.sp003876

Cited by 43 publications

(24 citation statements)

References 33 publications

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“…In a study in prepubertal pigs, comparable to our experiments, whilst i.v. injection of the non-selective COX inhibitor indomethacin attenuated both the LPS-induced fever and the LPS-induced rise of circulating concentrations of cortisol, indomethacin per se also caused a significant increase of plasma cortisol [31]. The discrepancy between these results and the results of our study may be due to the different drugs (indomethacin and diclofenac or meloxicam) or the different species (pig and guinea-pig).…”

Section: Discussioncontrasting

confidence: 96%

Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Roth

Hübschle

Pehl

et al. 2002

Pflugers Arch - Eur J Physiol

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Peripheral inflammatory stimuli result in the modification of a number of vital brain-controlled functions including the thermoregulatory set-point (induction of fever) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. We addressed the question of whether both of these components of the acute-phase response are induced by a common signal pathway. For this purpose we recorded body temperature (by remote radio-telemetry), HPA axis activity (circulating concentrations of cortisol by radio-immunoassay) and levels of the pro-inflammatory cytokines tumour necrosis factor and interleukin-6 (TNF, IL-6, using specific bioassays) in six groups of guinea-pigs. The animals received intra-arterial injections of either 10 microg/kg lipopolysaccharide (LPS) plus saline, 10 microg/kg LPS plus 5 mg/kg meloxicam (an inhibitor of the inducible form of cyclooxygenase), 10 microg/kg LPS plus 5 mg/kg diclofenac (a non-selective cyclooxygenase inhibitor), saline plus solvent, saline plus 5 mg/kg meloxicam or saline plus 5 mg/kg diclofenac. Injection of the cyclooxygenase inhibitors per se had no influence on the investigated parameters. Injection of LPS alone resulted in a biphasic fever, a more than fivefold increase in circulating cortisol and pronounced induction of TNF and IL-6. Treatment with the cyclooxygenase inhibitors either attenuated (meloxicam) or abolished (diclofenac) LPS-induced fever, but had no effect on the LPS-induced rise of plasma cortisol or IL-6. Circulating levels of TNF, in response to LPS, were enhanced by meloxicam and diclofenac, reflecting the negative feedback control exerted by prostaglandins on cytokine (specifically TNF) formation. These results provide the first evidence that the prostaglandin-dependent inflammatory pathway for fever induction is distinct from the pathway of HPA axis activation since fever, but not circulating cortisol, was attenuated by an inhibition of prostaglandin formation.

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Section: Discussioncontrasting

confidence: 96%

Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Roth

Hübschle

Pehl

et al. 2002

Pflugers Arch - Eur J Physiol

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“…The enhanced release of pituitary hormones induced by LPS can be suppressed by pretreatment with the cyclo-oxygenase inhibitor indomethacin, suggesting involvement of endogenous prostaglandins. 218 Dexamethasone has a similar action, inhibiting the cortisol response to LPS and lowering core temperature. 219 The corticosteroid synthesis inhibitor metyrapone also reduces LPS fever and inhibits the cortisol response to LPS.…”

Section: Non-cytokine Pathways: Cyclo-oxygenase Avp Leptin Estrogementioning

confidence: 99%

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

Beishuizen

Thijs

2003

Journal of Endotoxin Research

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Endotoxin is considered to be a systemic (immunological) stressor eliciting a prolonged activation of the hypothalamo-pituitary-adrenal (HPA) axis. The HPA-axis response after an endotoxin challenge is mainly due to released cytokines (IL-1, IL-6 and TNF-a) from stimulated peripheral immune cells, which in turn stimulate different levels of the HPA axis. Controversy exists regarding the main locus of action of endotoxin on glucocorticoid secretion, since the effect of endotoxin on this neuro-endocrine axis has been observed in intact animals and after ablation of the hypothalamus; however, a lack of LPS effect has been described at both pituitary and adrenocortical levels. The resulting increase in adrenal glucocorticoids has well-documented inhibitory effects on the inflammatory process and on inflammatory cytokine release. Therefore, immune activation of the adrenal gland by endotoxin is thought to occur by cytokine stimulation of corticosteroidreleasing hormone (CRH) production in the median eminence of the hypothalamus, which, in turn stimulates the secretion of ACTH from the pituitary. Acute administration of endotoxin stimulates ACTH and cortisol secretion and the release of CRH and vasopressin (AVP) in the hypophysial portal blood. During repeated endotoxemia, tolerance of both immune and HPA function develops, with a crucial role for glucocorticoids in the modulation of the HPA axis. A single exposure to a high dose of LPS can induce a long-lasting state of tolerance to a second exposure of LPS, affecting the response of plasma TNF-a and HPA hormones. Although there are gender differences in the HPA response to endotoxin and IL-1, these responses are enhanced by castration and attenuated by androgen and estrogen replacement. Estrogens attenuate the endotoxin-induced stimulation of IL-6, TNF-a and IL-1ra release and subsequent activation in postmenopausal women. There appears to be a temporal and functional relation between the HPA-axis response to endotoxin and nitric oxide formation in the neuro-endocrine hypothalamus, suggesting a stimulatory role for nitric oxide in modulating the HPA response to immune challenges. demonstrate higher plasma levels of IL-1 and TNF-a. Elevation of plasma glucocorticoids results in suppression of cytokines such as IL-1, IL-6, and TNF-a and in up-regulation of other cytokines, such as IL-4 and IL-10, and cytokine receptors. Thus, by regulation of cytokine production and action, the HPA axis contributes to modulation of the response to inflammation/infection. In addition, the role of HPA activation has been suggested to be a negative feedback system provided by the immunosuppressive activity of glucocorticoids, limiting inflammatory responses and preventing the immune system from over-reacting and causing tissue damage or autoimmunity.As early as 1957, Wexler et al. suggested that LPS could induce ACTH release since they found a depletion of ascorbic acid and cholesterol in the adrenal glands. 10 Moreover, LPS was not able to cause these changes in hypophysectomized rats. ...

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“…However, little is known about immune activation of the HPA axis during stress, and it is not clear whether activation of the HPA axis by acute stress alters neuroendocrine-immune interactions. While some studies have demonstrated that pigs reacted sensitively to endotoxin displaying sickness behaviour and physiological changes [11][12][13][14], there are few data on the endocrine and immune regulation of an acute inflammatory challenge during stress in pigs [15].…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine and Immune Responses to Acute Endotoxemia in Suckling and Weaned Piglets

Kanitz

Tuchscherer

et al. 2002

Neonatology

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The objective of this study was to characterize effects of weaning stress on behavioural, endocrine and immune responses to acute peripheral lipopolysaccharide (LPS) challenge in neonatal pigs. Weaning in 28-day-old piglets was accompanied by a significant increase in ACTH concentrations (p = 0.0378) and an increase in basal cortisol level (p = 0.0135). There was also a significant suppressive effect on lymphocyte proliferation in response to concanavalin A (p = 0.0048) in newly weaned piglets. Peripheral administration of LPS induced vomiting, diarrhoea and somnolence in both suckling and weaned piglets. The frequency of these signs of sickness was significantly higher in weaned piglets compared with suckling piglets (p = 0.0049). Additionally, LPS significantly increased plasma concentrations of TNF-α, cortisol and ACTH. While weaned piglets reacted to LPS with a higher release of ACTH (p = 0.0239) and cortisol (p = 0.0015) than suckling piglets there was no significant effect of weaning on the magnitude of TNF-α. The present data indicate that weaning suppresses the lymphocyte function, causes changes in endocrine regulation and has a substantial effect on the behavioural and endocrine response to an acute peripheral LPS challenge; consequently it could increase disease susceptibility.

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Cyclo‐oxygenase mediation of endotoxin‐induced fever, anterior and posterior pituitary hormone release, and hypothalamic c‐Fos expression in the prepubertal pig

Cited by 43 publications

References 33 publications

Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

Neuroendocrine and Immune Responses to Acute Endotoxemia in Suckling and Weaned Piglets

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