Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1) is a proinflammatory cytokine, alpha-MSH(1-13) molecules inhibit inflammation induced by cytokines, other mediators of inflammation, and by peripheral irritants. D-valine substitution in the antiinflammatory/antipyretic message sequence [alpha-MSH(11-13), Lys-Pro-Val] of alpha-MSH(1-13) increases the activity of the tripeptide. Our aim was to learn if D-valine substitution also enhances the antiinflammatory activity of the entire alpha-MSH(1-13) molecule and to determine if an antipyretic D-valine-substituted alpha-MSH(8-13) molecule is also antiinflammatory. Intraperitoneal injection of alpha-MSH(1-13) and of (D-Val13)alpha-MSH(1-13) caused dose-related suppression of ear edema induced in mice by intradermal injection of IL-1 beta; the two molecules were equipotent. (D-Val13)alpha-MSH(8-13) likewise inhibited inflammation, but the potency was less than that of the larger molecules. Intracerebroventricular injections of (D-Val13)alpha-MSH(1-13) and of the unsubstituted molecule were equipotent in reducing inflammation; the (D-Val13)alpha-MSH(8-13) molecule was less effective. The results support the idea that the alpha-MSH(1-13) molecule inhibits inflammation and suggest that the L-conformation of alpha-MSH(1-13) is maximally effective with regard to its antiinflammatory activity. The results with alpha-MSH(8-13) are consistent with previous findings of lesser antihost response activity of alpha-MSH fragments that contain the COOH-terminal tripeptide Lys-Pro-Val.
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PMID:Inhibition of IL-1 beta-induced peripheral inflammation by peripheral and central administration of analogs of the neuropeptide alpha-MSH. 839 57

IL-1 is a pro-inflammatory cytokine which controls many features of the immune and inflammatory response. When injected into a mouse 6-day-old air-pouch, human rIL-1 (1 to 100 ng) induced in a dose-dependent fashion a migration of PMN that could be reliably assessed 4 h after injection. Both IL-1 alpha and IL-1 beta were active in this model. The effect of the cytokine was inhibited by local administration of actinomycin D (1 to 10 micrograms), alpha-melanocyte-stimulating hormone (200 micrograms), and a mAb recognizing IL-1R type I (10 micrograms). Indomethacin (1 mg/kg), an inhibitor of cyclo-oxygenase, and BW4AC (2 mg/kg), a selective lipoxygenase inhibitor, were without effect but moderate inhibition was seen with the platelet-activating factor antagonist WEB2086 (1 to 10 mg/kg). The glucocorticoid dexamethasone (0.015 to 1.5 mg/kg) potently inhibited the elicitation of neutrophils induced by IL-1 when given systemically 2 h before the cytokine. The steroid-induced anti-inflammatory protein lipocortin 1 (LC1) also produced a dose-dependent inhibition of PMN migration into the pouch with an ED50 of approximately 0.15 to 0.21 mg/kg. The denatured protein was without effect. Passive immunization of mice with a polyclonal sheep antiserum or a mAb raised against LC1 abolished the inhibitory action of dexamethasone whereas preimmune serum or control IgG were without significant effect. These findings provide further evidence that LC1 is involved in the anti-inflammatory action of glucocorticosteroids and suggest that this protein may act as an endogenous regulator of IL-1 action.
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PMID:Modulation of IL-1-induced neutrophil migration by dexamethasone and lipocortin 1. 842 49

There is now considerable evidence that nitric oxide (NO) is an important neuroregulatory agent, but there has been very little investigation of the possible role of NO in neuroendocrine mechanisms. We have previously shown that acute rat hypothalamic explants can be used to study the regulation of hypothalamic neuropeptide release, and we have now utilised this experimental approach to investigate the putative involvement of NO in the control of the principal corticotropin-releasing hormone, CRH. We studied the direct effects of the NO precursor L-arginine (L-ARG), as well as the NO donors molsidomine and sodium nitroprusside, on both the basal and stimulated release of CRH; the stimuli used were non-specific depolarisation with potassium chloride (KCl) and the specific cytokine, interleukin-1 beta (IL-1 beta; 100 U/ml). L-ARG was tested in each experimental condition with and without contemporaneous addition of its competitive antagonist NG-monomethyl-L-arginine (L-NMMA). IL-1 beta-induced CRH release was also investigated in the presence of D-arginine (D-ARG), which is not active as a precursor to NO, and ferrous hemoglobin (Hb), a substance which is a potent inactivator of NO. None of the NO precursors (L-ARG, molsidomine, sodium nitroprusside) or antagonists (L-NMMA or Hb) was able to affect basal CRH release. However, L-ARG 10 and 100 microM were found to significantly inhibit the release of CRH induced by 40 mM KCl; CRH fell to 45% of its stimulated level at the higher dose of L-ARG. This effect was attenuated in the presence of L-NMMA at a ten-fold higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro. 848 68

Exposure to an antigen causes significant endocrine changes, some of which in turn affect immune functioning. Proteins produced by activated immune cells, cytokines, act as messengers between the immune and the endocrine systems, and convey to the brain the occurrence of immune activation. We have investigated the ability of interleukin 1 (IL-1) alpha and beta to alter endocrine functioning in the adult rat. Acute peripheral injection of IL-1 alpha or beta causes dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone secretion. These changes are primarily dependent upon increased release of corticotropin-releasing factor (CRF) into the portal circulation, and recent studies have indicated that the paraventricular nucleus (PVN) of the hypothalamus is the main source of this CRF. This conclusion is based on our finding that intravenous injection of IL-1 increases CRF biosynthesis in the PVN, and that lesion of this hypothalamic area interferes with IL-1's stimulatory action on ACTH secretion. Indomethacin partially reverses the effect of IL-1, suggesting that increased prostaglandin synthesis plays some part in this activation. Administration of IL-1 beta into the brain, but not into the general circulation, interferes with secretion of luteinizing hormone (LH) and ovulation through mechanisms involving endogenous opiates. Because neither CRF antagonists, nor lesions of the PVN, alter the inhibitory effect of IL-1 on LH release, CRF perikarya in the PVN do not appear to be involved in this phenomenon. Central administration of IL-1 beta strongly increases c-Fos immunoreactivity in the PVN, mainly within CRF neurons. Infusion of IL-1 beta into the PVN does not induce measurable changes in release of gonadotropin-releasing hormone (GnRH), but infusion of IL-1 directly into the median preoptic area (MPOA), a region rich in GnRH perikarya, markedly decreases GnRH secretion in rats bearing a push-pull cannula in the median eminence. Furthermore, central administration of IL-1 beta during the critical phase of pro-oestrus (1600-1930) also inhibits the expression of c-fos in GnRH cell bodies in the MPOA. Thus, we suggest that IL-1 interferes with reproductive functioning through a direct action at the level of the MPOA. These results indicate that circulating cytokines can alter the activity of the hypothalamo-pituitary-adrenal axis by increasing CRF release, probably through both immediate stimulation of CRF terminals within the median eminence and stimulation of CRF synthesis in the PVN. In contrast, cytokine-induced changes in LH and GnRH secretion are mediated through pathways lying primarily beyond the blood-brain barrier.
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PMID:Mechanisms mediating the effects of cytokines on neuroendocrine functions in the rat. 849 Oct 87

The purpose of this study was to investigate the effects of circulating interleukin-1 beta (IL-1 beta) on the release of norepinephrine (NE) in the paraventricular nucleus (PVN). After intraperitoneal administration of IL-1 beta, NE was measured by high performance liquid chromatography in the perfusate collected from the PVN of conscious, freely moving rats by the technique of push-pull perfusion. IL-1 beta produced an increase in NE release. Both the strength and duration of NE release were dose-dependent. It is concluded that circulating IL-1 beta activates the noradrenergic innervation to the PVN and that this is part of the mechanism by which it stimulates the release of the corticotropin-releasing hormone (CRH) and produces its other neuroendocrine and central effects.
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PMID:Systemic administration of interleukin-1 stimulates norepinephrine release in the paraventricular nucleus. 850 61

It is well established that corticotropin-releasing hormone (CRH) is a principal neuropeptide which mediates the adrenocorticotropic hormone (ACTH) secretory response to interleukin (IL)-1 in the rat. It has recently been suggested that besides CRH, arginine vasopressin may also play a stimulatory role in IL-1 induced ACTH secretion. However, it remains to be elucidated whether other neuropeptides possessing an ACTH-releasing activity are involved in this neuroendocrine event. Therefore, in this study, we examined possible roles for oxytocin (OT) and cholecystokinin (CCK)-8 in the IL-1-induced ACTH response, utilizing the technique of immunoneutralization of these peptides. For comparison, we examined the effect of CRH immunoneutralization as well. Human recombinant IL-1 beta (50 ng) was given intracerebroventricularly (to the 3rd ventricle) to freely moving male rats 15 min after injecting specific antiserum against CRH, OT, or CCK-8, or normal rabbit serum (control) via the same route. As expected, anti-CRH antibody significantly suppressed the ACTH response to IL-1 beta. Interestingly, anti-OT antibody acted in the same manner, whereas anti-CCK-8 antibody did not. These results suggest that in addition to CRH and arginine vasopressin, OT may also play a significant role in mediating the IL-1 beta-induced ACTH secretion in the rat.
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PMID:Involvement of oxytocin and cholecystokinin-8 in interleukin-1 beta-induced adrenocorticotropin secretion in the rat. 852 Nov 44

To explore the interactions between the hypothalamic-pituitary-adrenocortical axis and the immune system under stress conditions, we used an experimental rat model for chronic tail-restraint devised earlier for ground studies in space physiology. The system was used in two positions: (1) the orthostatic restraint position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs had been raised by a head-down tilt. After 7 days of either restraint, sequential blood samples were taken via an indwelling aortic cannula, before and at various time intervals between 15 and 300 min after an intravascular infusion of 25 micrograms/kg lipopolysaccharide (LPS). The plasma titers of adrenocorticotropin (ACTH), corticosterone (CORT) and interleukin-1 beta (IL-1 beta) were assayed. Under basal conditions, both OR and AOR restraints induced a 5-fold increase in IL-1 beta with no significant changes in ACTH and CORT levels. A robust increase in all three variables was observed after LPS injection. However, the IL-1 beta response to LPS was significantly higher in both restrained groups than in controls. Both the amplitude and the percentage of individually restrained rats displaying elevated IL-1 beta levels were increased up to 5 h. In contrast, the ACTH and CORT post-LPS responses were normal in the OR group. They were unusually dissociated in the AOR rats, which displayed depressed ACTH levels associated with slightly increased CORT levels. Our results suggest that immune-neuroendocrine responses to chronic restraint stress may differ from those generally observed in acute stress.
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PMID:Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release. 852 95

The presence of immunoreactive pro-opiomelanocortin (POMC)-derived peptides (adrenocorticotropin hormone, beta-endorphin, alpha-melanocyte-stimulating hormone) and of cytokine-like molecules [interleukin (I)-1 alpha, IL-1 beta, IL-2, Il-6, tumour necrosis factor-alpha] was demonstrated in periodic acid-Schiff-positive epithelial cells in the thymus of the goldfish (Carassius c. auratus) using immunocytochemical procedures. POMC-derived peptide- and cytokine-like molecules were localized in the same cell type. Lymphocytes were negative for all the above mentioned molecules. Despite the smaller number of cells positive for neuropeptide- and cytokine-like molecules, our findings suggest that immune-neuroendocrine interactions are likely to occur in the thymus of goldfish.
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PMID:Evidence for the presence of immunoreactive POMC-derived peptides and cytokines in the thymus of the goldfish (Carassius c. auratus). 855 Mar 79

It is well known that interleukin (IL)-1 is a potent activator of the hypothalamo-pituitary-adrenal axis in the rat. Many studies have reported that prostaglandins (PGs), especially PGE2, in the brain may mediate the IL-1 stimulation of corticotropin-releasing hormone release, which then leads to adrenocorticotropin (ACTH) secretion. However, a general consensus has yet to emerge regarding whether PGE2 is the only or the most important PG in the brain mediating IL-1-induced ACTH secretion in the rat. To address this question, we examined the effect of intracerebroventricular (icv) administration of antisera against PGE1, PGE2 or PGF2 alpha, or normal rabbit serum on the ACTH response induced by an icv injection of IL-1 beta in the rat. Each antibody or normal rabbit serum (as the control) was given icv 15 min before an icv administration of human recombinant IL-1 beta (50 ng). IL-1 beta produced a significant rise in plasma ACTH levels, and this response was significantly suppressed by either of the three PG antibodies. Interestingly, the inhibitory effect of anti-PGE2 antibody seemed to be somewhat weaker than those of the other two antibodies. We conclude that not only PGE2 but also PGE1 and PGF2 alpha in the brain may mediate the IL-1 beta stimulation of ACTH secretion in the rat.
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PMID:Role of prostaglandins E1, E2 and F2 alpha in the brain in interleukin 1 beta-induced adrenocorticotropin secretion in the rat. 858 Mar 80

The effects of microinjections of recombinant human interleukin-1 beta (rhIL-1 beta) into the hypothalamus and neighboring basal forebrain on nociceptive behavior were studied using a hot-plate test in rats. The microinjection of rhIL-1 beta at doses between 5 pg/kg and 50 pg/kg into the medial part of the preoptic area (MPO) reduced the paw-withdrawal latency. The maximal reduction was obtained 30 min after the injection of rhIL-1 beta at 20 pg/kg. RhIL-1 beta (20 pg/kg)-induced hyperalgesia was completely blocked by the simultaneous injection of IL-1 receptor antagonist (IL-1ra, 20 ng/kg), Na salicylate (200 ng/kg) or alpha-melanocyte-stimulating hormone alpha-MSH, 20 ng/kg). The intra-MPO injection of rhIL-1 beta at doses of less than 5 pg/kg or more than 50 pg/kg (up to 2 ng/kg) into the paraventricular nucleus, the lateral hypothalamic area and the septal nucleus had no effect on nociception. The microinjection rhIL-1 beta (20 pg/kg-50 pg/kg) into the ventromedial hypothalamus produced a prolongation of the paw-withdrawal latency. A maximal prolongation was obtained 10 min after the injection of rhIL-1 beta at 50 pg/kg. This reaction was also blocked by the simultaneous injection of IL-1ra (50 ng/kg) and Na salicylate (500 ng/kg). These findings indicate that IL-1 beta in the MPO and the VMH produces hyperalgesia and analgesia, respectively, while, in addition, both effects are mediated by IL-1 receptors and the synthesis of prostaglandins.
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PMID:The opposing effects of interleukin -1 beta microinjected into the preoptic hypothalamus and the ventromedial hypothalamus on nociceptive behavior in rats. 862 21


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