Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant arthritis (AA) in the rat leads to chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the loss of its diurnal rhythmicity. We have investigated the effects of adrenalectomy (ADX) and different levels of corticosterone replacement upon plasma ACTH levels and anterior pituitary pro-opiomelanocortin (POMC), GH and prolactin mRNAs during the development of AA. In control ADX animals, we observed the negative feedback effects of exogenous corticosterone on plasma ACTH and anterior pituitary POMC mRNA. In the ADX animal with AA, however, the increased POMC mRNA which was observed was not reduced by exogenous corticosterone on day 7 of AA, although the negative feedback effect of corticosterone on plasma ACTH was intact. On day 14, however, even high dose corticosterone replacement failed to have a significant feedback effect on the raised levels of plasma ACTH. In control ADX animals, corticosterone replacement resulted in increased anterior pituitary GH mRNA and reduced prolactin mRNA. In contrast, in ADX animals with AA, GH mRNA was reduced and there was a further decrease in prolactin mRNA. In these animals, corticosterone replacement did not affect GH or prolactin mRNA expression. These data demonstrate a disruption of the normal mechanisms underlying feedback inhibition of the HPA axis by glucocorticoids during AA. Similarly, the glucocorticoid-dependent regulation of GH and prolactin mRNA expression is altered in AA.
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PMID:Glucocorticoid-mediated responses of plasma ACTH and anterior pituitary pro-opiomelanocortin, growth hormone and prolactin mRNAs during adjuvant-induced arthritis in the rat. 133 26

1 Peritoneal macrophages (M phi) collected from adrenalectomized (ADX) rats released more interleukin-1 (IL-1) activity and prostaglandin E2 (PGE2) than macrophages from sham-operated (SHO) rats. 2 The increase in IL-1 activity in the supernatants was confirmed by the increase of the cell-associated 33 kD IL-1 alpha precursor in ADX macrophages stimulated by lipopolysaccharide (LPS). 3 After the injection of Complete Freund's Adjuvant (CFA) to induce adjuvant arthritis, 60% of the ADX rats died, while no deaths occurred in the SHO group. 4 The in vivo administration of dexamethasone inhibited both IL-1 and PGE2 release by macrophages as well as protecting ADX animals from CFA-induced death. Indomethacin and BW 755C partially protected the animals from this lethal effect. 5 These results suggest that adrenalectomy induces an increased release of IL-1 both in vitro and in vivo, and are consistent with a feedback mechanism between IL-1 and glucocorticoid hormones.
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PMID:The effect of adrenalectomy on interleukin-1 release in vitro and in vivo. 251 46

Adjuvant-induced arthritis (AA) in specific strains of rats is an immunologically mediated inflammatory disease which is also characterised by activation of the endocrine system. To further investigate the effects of AA on processing of the pro-opiomelanocortin (POMC) precursor in rat immune tissues, we utilised radioimmunoassays for adrenocorticotrophin (ACTH), beta-endorphin and alpha-melanocyte-stimulating hormone (alpha-MSH) to measure these peptides in the spleen and thymus. 14 days following adjuvant injection, spleen levels of ACTH were elevated in the AA group (4.47 +/- 1.04 ng/g tissue, n = 9) compared to controls (2.42 +/- 0.4 ng/g) and exacerbation of the disease by removal of circulating glucocorticoids through bilateral adrenalectomy (ADX) resulted in further elevation of spleen ACTH (5.11 +/- 1.22 ng/g). beta-Endorphin levels in both the AA (10.60 +/- 1.61 ng/g) and AA/ADX (13.37 +/- 2.36 ng/g) groups were higher than controls (5.57 +/- 0.65 ng/g). Conversely, alpha-MSH spleen levels were decreased in the AA (2.89 +/- 0.22 ng/g) and AA/ADX (2.22 +/- 0.33 ng/g) groups compared to controls (4.62 +/- 0.45 ng/g) and were also decreased following adrenalectomy. In the thymus, ACTH levels were elevated in the AA group (8.95 +/- 1.41 ng/g) compared to controls (5.79 +/- 0.63 ng/g), and the same pattern was evident for thymic alpha-MSH (0.64 +/- 0.08 ng/g in AA animals compared to control levels of 0.35 +/- 0.03 ng/g). Following G50 gel filtration, ACTH and beta-endorphin immunoreactivities (ir) were present in both spleen and thymus as two peaks, one which eluted near the void volume and one which eluted in a lower molecular mass position than the standards.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a chronic inflammatory stress on levels of pro-opiomelanocortin-derived peptides in the rat spleen and thymus. 829 57

During development of adjuvant arthritis (AA) in the rat, anterior pituitary interleukin-6 (IL-6) mRNA expression was increased. Following adrenalectomy and AA there was a further increase in the accumulation of pituitary IL-6 transcript. Corticosterone (B) replacement in adrenalectomized (ADX) animals resulted in a dose-dependent reduction in pituitary IL-6 mRNA accumulation, while in ADX plus AA animals these effects of B were less marked. Cyclosporine A (CsA) markedly reduced the AA-induced increase in IL-6 mRNA. These data are consistent with an immunologically-mediated activation of pituitary IL-6 mRNA in AA, which may contribute to the increased activity of the pituitary-adrenal axis seen in this condition.
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PMID:Effects of glucocorticoids and chronic inflammatory stress upon anterior pituitary interleukin-6 mRNA expression in the rat. 834 65

We have developed an extraction method and radioimmunoassay for the measurement of interleukin-1 beta (IL-1 beta) in rat tissues, using an antibody specific for IL-1 beta, IL-1 beta was detected in the spleen and thymus of control rats. Adrenalectomy (ADX) had no effect upon control levels of IL-1 beta. In animals with adjuvant-induced arthritis, IL-1 beta content in the spleen and thymus increased after 14 days. These increases in tissue IL-1 beta contents were not evident in ADX arthritic animals. We conclude that IL-1 beta synthesis is stimulated in tissues of the immune system following the development of adjuvant-induced arthritis. Failure to observe elevated levels of tissue IL-1 beta in ADX arthritic rats may be evidence for tissue depletion due to increased IL-1 beta release in the absence of circulating corticosteroids.
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PMID:Interleukin-1 beta measured by radioimmunoassay in the rat spleen and thymus is increased during chronic inflammatory stress. 835 Sep 80

In vertebrates, thyroid hormone and its cognate nuclear receptors are involved in a complex arrangement of physiological and developmental function. Since thyroid hormone has also been shown to affect immune responses, we investigated the DNA binding status of T3 receptors of spleen nuclear extracts in a) rats with adjuvant arthritis (AA); b) adrenalectomized rats (ADX), and c) animals with adjuvant arthritis followed by adrenalectomy (AA + ADX). A marked diminution in the functional binding of nuclear thyroid hormone receptors to DR4 thyroid hormone responsive DNA element was found in the spleens of AA and AA + ADX rats when compared to a control group or ADX rats. The data based on in vivo experiments suggest that the nuclear receptor--thyroid hormone responsive element complex status within the cell nucleus may be altered in adjuvant arthritis.
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PMID:Adjuvant arthritis in the rat is associated with decreased binding of nuclear receptors to thyroid hormone responsive element in spleen extracts. 1019 19

Possible contributions of the hypothalamo-hypophyseal-adrenal axis to the development of adjuvant-induced arthritis and therapeutic actions of the prototypical kappa-opioid agonist PNU-50,488H (PNU-50) were studied in DA rats. Paw edema, nociception, histological and radiological joint damage, and tumor necrosis factor-alpha release by peritoneal macrophages were measured in adrenalectomized (ADX) and sham-operated (SHO) arthritic animals (drug-treated and untreated groups). Disease developed earlier in ADX rats (paw edema was first apparent 11 days postadjuvant compared with day 13 in SHO animals) and remained more severe in that group. Twice-daily PNU-50 treatment completely prevented the development of edema in the SHO group but was effective in the ADX animals only on day 18. PNU-50 substantially reduced the pooled severity index (combined quantitative edema, histological and radiological assessments) at day 18 in both SHO and ADX rats and to an equal extent. During disease development, the paws of SHO, but not ADX, rats became hyperalgesic; paradoxically, ADX animals were hyperalgesic during PNU-50 treatment, but the drug produced analgesia in SHO animals. Compared with cells harvested from healthy animals, macrophages from arthritic rats released about twice as much tumor necrosis factor-alpha after lipopolysaccharide stimulation. It was concluded that the hypothalamo-hypophyseal-adrenal axis influences the development of adjuvant arthritis and plays a partial role in the therapeutic action of the kappa-agonist PNU-50.
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PMID:The importance of the hypothalamo-hypophyseal-adrenal axis to the anti-inflammatory actions of the kappa-opioid agonist PNU-50,488H in rats with adjuvant arthritis. 1094 69