Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat

Turnbull, Andrew V.; Dow, R. C.; Hopkins, Stephen J.; White, Anne; Fink, George; Rothwell, Nancy J.

doi:10.1016/0306-4530(94)90006-x

Cited by 49 publications

(34 citation statements)

References 29 publications

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“…In mice ACTH is a necessary permissive factor that enables IL6 to stimulate glucocorticoid secretion, at least during the first 36 h of viral infection (7). In both humans and animals, during inflammatory response or IL6 treatment, dissociation between central activation of the HPA axis and the adrenal cortex secretion is found (14,(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Žarković

Ignjatović

Dajak³

et al. 2008

European Journal of Endocrinology

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Objective: Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitaryadrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Design and methods: Basal IL6 concentration was measured and a low dose (1 mg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. Results: Data are presented as meanGS.E.M. Basal IL6 level was 0.84G0.10 pg/ml. Basal cortisol was 351.9G18.3 nmol/l. Maximal cortisol during synacthen test was 653.0G20.6 nmol/l. Maximal cortisol increment was 301.1G20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (rZ0.63, 95% confidence interval) 0.42-0.83). Conclusions: In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions. European Journal of Endocrinology 159 649-652

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Section: Discussionmentioning

confidence: 99%

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Žarković

Ignjatović

Dajak³

et al. 2008

European Journal of Endocrinology

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“…Inflammation was induced by the intramus- cular injection of turpentine, which produces an initial transient (1-2 hr after injection) series of physiological responses (elevation in body temperature, hypermetabolism, activation of the HPA axis) attributable to nociceptive afferent inputs (Cooper and Rothwell, 1991;Turnbull et al, 1994;Turnbull and Rivier, 1996a). This is followed by a full-blown APR that commences at ϳ3-4 hr, lasts for at least 24 hr, and is mediated, at least in part, by a number of cytokines, e.g., IL-1, IL-6, and TNF-␣ (Oldenburg et al, 1993;Cooper et al, 1994a;Kopf et al, 1994;Turnbull et al, 1994;Zheng et al, 1995;Turnbull and Rivier, 1996a). Here we demonstrate that inhibition of TNF-␣ action specifically within the brain markedly reduces the ACTH response that is apparent 3.0 -7.5 hr after turpentine administration.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, increases in cerebral cytokine synthesis may occur at times other than those adopted in the present study. But since the regions of the brain (hypothalamus, hippocampus, cortex) and pituitary sampled by the most sensitive technique (SQ-PCR) are those most implicated in the regulation of neuroendocrine functions, and many of the APRs (e.g., fever, hypermetabolism, HPA activation) to local inflammation induced by turpentine peak at ϳ8 hr (Cooper and Rothwell, 1991;Cooper et al, 1994a;Turnbull et al, 1994;Turnbull and Rivier, 1996a), we believe it highly unlikely that elevated cytokine synthesis within the CNS contributes to the ensuing APRs. In particular, the markedly suppressive effects of inhibition of TNF-␣ action within the brain that we demonstrate here seem not to be caused by elevated TNF-␣ synthesis within the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Sterile local inflammation was induced in the hindlimb by intramuscular injection of 50 l of turpentine/100 gm body weight into the left thigh muscles (Turnbull et al, 1994;Turnbull and Rivier, 1996a). This produced a pronounced swelling of the limb that was evident ϳ3-4 hr after injection.…”

Section: Methodsmentioning

confidence: 99%

“…The present study sought to determine the role of cytokines within the brain in the mediation of the HPA axis response to a peripheral, discrete tissue inflammation in the rat (Turnbull et al, 1994;Turnbull and Rivier, 1996a). Because of the proximal nature of TNF-␣ in the generation of cytokines and subsequent responses, our study focused on this cytokine.…”

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confidence: 99%

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Inhibition of Tumor Necrosis Factor-α Action within the CNS Markedly Reduces the Plasma Adrenocorticotropin Response to Peripheral Local Inflammation in Rats

et al. 1997

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The present study tested the hypothesis that the cytokine tumor necrosis factor-α (TNF-α) is an important CNS mediator of the hypothalamo-pituitary-adrenal (HPA) axis response to local inflammation in the rat. Recombinant murine TNF-α administered directly into the cerebroventricles of normal rats produced a dose-dependent increase in plasma adrenocorticotropin (ACTH) concentration. Local inflammation induced by the intramuscular injection of turpentine (50 μl/100 gm body weight) also produced an increase in plasma ACTH, peaking at 160–200 pg/ml at 7.5 hr after injection (compared with 10–30 pg/ml in controls). Intracerebroventricular pretreatment with either 5 μl of anti-TNF-α antiserum or 1–50 μg of soluble TNF receptor construct (rhTNFR:Fc) reduced the peak of the ACTH response to local inflammation by 62–72%. In contrast, intravenous treatment with the same doses of anti-TNF-α or rhTNFR:Fc had no significant effect on the ACTH response to local inflammation. Although these data indicated an action of TNF-α specifically within the brain, no increase in brain TNF-α protein (measured by bioassay) or mRNA (assessed using eitherin situhybridization histochemical or semi-quantitative RT-PCR procedures) was demonstrable during the onset or peak of HPA activation produced by local inflammation. Furthermore, increased passage of TNF-α from blood to brain seems unlikely, because inflammation did not affect plasma TNF-α biological activity. Collectively these data demonstrate that TNF-α action within the brain is critical to the elaboration of the HPA axis response to local inflammation in the rat, but they indicate that increases in cerebral TNF-α synthesis are not a necessary accompaniment.

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Time-course study of the Golgi-lysosome region of rat hepatocytes during early acute phase response to inflammation

Thorne-Tjomsland

Jamieson

1996

Anat. Rec.

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Background In a previous study of the hepatocyte Golgi apparatus 24 hr following the induction of the acute phase response to inflammation, it was found that the predominant secretory content was a granulofilamentous material (GFM), rather than lipoprotein particles (LP) as in controls (Thorne‐Tjomsland and Jamieson, 1995, Anat. Rec., 241:439–450). The present study aimed to determine when and how this switch occurs and to monitor the Golgi‐lysosome region of hepatocytes in general during early inflammation. Methods Rats were injected with turpentine oil as an inflammatory agent. At 1, 2, 6, 12, and 16 hr after turpentine‐injection (TI), the livers were prefixed by perfusion with cacodylate‐buffered glutaraldehyde, postfixed with ferrocyanide reduced osmium, and processed for thin section transmission electron microscopy. Results LP were processed at all time points between 1 and 16 hr post‐TI, and at 1 and 2 hr post‐TI, the Golgi stacks were engorged with LP and therefore apparently processed more of these particles than in controls. A GFM was processed at later time points, starting at 12 hr post‐TI. At the two time points when LP and GFM were co‐processed, these materials were frequently seen sorted from each other within the trans‐saccule and/or the trans‐Golgi network (TGN). At the level of the TGN, these materials were packaged into secretory vesicles which typically contained LP and/or GFM. Massive depletion of cytoplasmic glycogen was observed primarily at 1, 2, and 6 hr following TI. Concomitantly and temporarily, glycogen accumulated within Golgi‐associated lysosome‐like bodies with extensive appendages. Conclusions The switch in Golgi apparatus secretory content from LP to GFM occurred at around 12 hr post‐TI, but was not discrete. The initial appearance of the GFM coincided with the initial increase in the serum of hepatocyte‐derived acute phase reactants (see review Schreiber et al., 1989, Ann. NY Acad. Sci., 557:61–85). An additional and surprising finding of the present study was that significant changes occurred in the Golgi‐lysosome region much prior to the onset of acute phase reactant synthesis: 1 and 2 hr post‐TI, the Golgi processed above‐normal amounts of LP and Golgi‐associated, lysosome‐like bodies sequestered glycogen. © 1996 Wiley‐Liss, Inc.

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Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat

Cited by 49 publications

References 29 publications

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans

Inhibition of Tumor Necrosis Factor-α Action within the CNS Markedly Reduces the Plasma Adrenocorticotropin Response to Peripheral Local Inflammation in Rats

Time-course study of the Golgi-lysosome region of rat hepatocytes during early acute phase response to inflammation

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