Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) act centrally to affect eating behavior and thermoregulation and may be involved in the physiological mechanisms leading to anorexia, adipsia and loss in body weight. The newly discovered macrophage inflammatory protein-1 (MIP-1) infused into the anterior hypothalamic, preoptic area (AH/POA) evokes an intense hyperthermia. The present experiments were designed to determine whether MIP-1 affects the feeding mechanism in the ventromedial hypothalamus (VMH) independently of the thermoregulatory mechanism in the AH/POA. For the microinjection of MIP-1, guide cannulae were implanted stereotaxically in the rat just above the VMH or AH/POA. Following postoperative recovery, each unrestrained rat was adapted to procedures whereby body temperature and intakes of food and water available ad lib were monitored at predetermined intervals. When an efficacious dose of 5.6 picograms (pg) MIP-1 was microinjected in a volume of 0.5 microliters into the VMH, the intake of food in the rat was reduced significantly in the short term and throughout the following 22 h. Within intervals of 30 min and 4.0 h following MIP-1, the amount of food consumed was 4.0 and 10 g, respectively, below that eaten by control rats given the saline solvent vehicle injected at the same site in the VMH. Over the entire test period, the intake of water was similarly significantly below that of the control rats. Whereas MIP-1 injected into the AH/POA evoked fever accompanied by a transient decline in feeding, the body temperature of the rats was unaffected by the cytokine injected in the VMH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anorexia and adipsia: dissociation from fever after MIP-1 injection in ventromedial hypothalamus and preoptic area of rats. 174 16

The purpose of this study was to clarify the central site of action as well as functional characteristics of the febrile response of the cytokine, macrophage inflammatory protein-1 (MIP-1). Guide cannulae for microinjection were implanted stereotaxically in the rat just above the pyrogen and thermosensitive area of the anterior hypothalamic, preoptic area (AH/POA). Following postoperative recovery, the body temperature of each rat (Tbo) was monitored during an experiment by a colonic thermistor probe at 0.5-1.0-h intervals. When MIP-1 was microinjected in a 0.5-microliter volume into the AH/POA in one of eight concentrations ranging from 0.0028 nanograms (ng) to 9.0 ng, an intense monophasic or biphasic fever was evoked. The MIP-1-induced increase in the Tbo of the rat was characterized by its short latency of 15 to 30 min and an inverse dose-response curve. Measures of mean latency and maximal rise in Tbo following MIP-1 confirmed the potency of this dose. Although the dose of 0.028 ng produced a fever of over 2.0 degrees C with a latency of only 15 min or less, the hyperthermic response became less intense as the dose of MIP-1 was increased. An anatomical mapping of sites of microinjection which reacted to MIP-1 in mediating fever revealed that the medial portion of the POA of the rat just rostral to the border of the AH was the region of maximum sensitivity to the cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever induced by macrophage inflammatory protein-1 (MIP-1) in rats: hypothalamic sites of action. 175 89

This investigation examined the extent to which the activity of a prostaglandin (PG) in the anterior hypothalamic, preoptic area (AH/POA) of the rat plays a role in the intense fever induced by macrophage inflammatory protein-1 (MIP-1) applied directly to this anatomical region. For the microinjection of both a PG synthesis inhibitor, indomethacin, and MIP-1 into sites within the AH/POA, guide cannulae were implanted chronically just above this pyrogen-reactive region. Postoperatively, the body temperature (Tb) of each rat was monitored in the unrestrained condition by means of a colonic thermistor probe. MIP-1 microinjected into the AH/POA in a 0.5-microliter volume evoked a biphasic fever when given in a dose of 5.6 picograms (pg) and a monophasic fever in a dose of 28 pg. The latency of the febrile response was ordinarily 15 min with an asymptote of 1.5 degrees C reached ordinarily within 2.0-2.5 h. When the cytokine-reactive site in the AH/POA was pretreated with indomethacin microinjected in an efficacious dose of 0.5 microgram, the MIP-1 fever evoked by 5.6 pg was not inhibited. Further, pretreatment of AH/POA sites with indomethacin prior to the higher 28-pg dose of MIP-1 delayed the febrile response but did not block it. As a systemic control, indomethacin also was administered intraperitoneally in a dose of 5.0 mg/kg, again 15 min prior to the microinjection of MIP-1 into the AH/POA. In this case, indomethacin only partially attenuated but did not block the fever evoked by either dose of MIP-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothalamic indomethacin fails to block fever induced in rats by central macrophage inflammatory protein-1 (MIP-1). 194 95

Macrophage inflammatory protein (MIP-1) administered systemically causes a fever not blocked by a prostaglandin (PGE) synthesis inhibitor. The purpose of this study was to examine the central mechanism of pyrexic action of this cytokine in the unrestrained rat. After guide cannulae for microinjection were implanted stereotaxically just above the anterior hypothalamic preoptic area (AH/POA), the body temperature of each rat was monitored by a colonic thermistor probe. Saline control vehicle or MIP-1 was microinjected into the AH/POA in one of eight concentrations ranging from 0.0028-9.0 ng per 0.5 mu 1 volume. MIP-1 induced a biphasic or monophasic fever of short latency characterized by an inverse dose-response curve. The potency of MIP-1 was in the femtomolar (10(-15)) range with the lowest dose of 0.028 ng producing a fever of over 2.0 degrees C with a latency of 15 min or less. To determine whether a PGE mediates MIP-1 fever, indomethacin was administered either intraperitoneally in a dose of 5.0 mg/kg or directly into the MIP-1 injection site in a dose of 0.5 microgram/0.5 mu 1, both injected 15 min before MIP-1. Pretreatment of the injection site in the AH/POA with indomethacin failed to prevent the febrile response evoked by MIP-1 injected at the same locus. Further, the dose of systemic indomethacin, which blocks PGE-induced fever in the rat, attenuated only partially the MIP-1 fever. The results demonstrate that MIP-1 is the most potent endopyrogen discovered thus far, and that its action is directly in the region of the hypothalamus which contains both thermosensitive and pyrogen-sensitive neurons. The local action of MIP-1 on cells of the AH/POA in evoking fever is unaffected by the PGE inhibitor which indicates, therefore, that a cellular mechanism operates in the hypothalamus to evoke fever independently of the central synthesis of a PGE.
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PMID:Macrophage inflammatory protein-1: unique action on the hypothalamus to evoke fever. 219 77

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr, 6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta). 780 90

The role of a prostaglandin of the E series (PGE) in the hypothalamic mechanisms underlying a fever continues to be controversial. This paper reviews the historical literature and current findings on the central action of the PGEs on body temperature (Tb). New experiments were undertaken to examine the local effect of muscarinic, nicotinic, serotonergic, alpha-adrenergic, or beta-adrenergic receptor antagonists at hypothalamic sites where PGE1 caused a rise in Tb of the primate. Guide tubes for microinjection were implanted stereotaxically above sites in and around the anterior hypothalamic, preoptic area (AH/POA) of male Macaque monkeys. Following postoperative recovery, 30-100 ng of PGE1 was micro-injected unilaterally in a volume of 1.0-1.5 microliter at sites in the AH/POA to evoke a rise in Tb, and once identified, pretreated with a receptor antagonist. PGE1 hyperthermia was significantly reduced by microinjections of the muscarinic and nicotinic antagonists, atropine, or mecamylamine, at PGE1 reactive sites in the AH/POA. The serotonergic antagonist, methysergide, injected at PGE1 sensitive sites in the ventromedial hypothalamus also attenuated the rise in Tb. However, the 5-HT reuptake blocker, fluoxetine, and the beta-adrenergic receptor antagonist, propranolol, injected in the AH/POA failed to alter the PGE1 hyperthermia. In contrast, the alpha-adrenergic antagonist, phentolamine, potentiated the increase in Tb at all PGE1 reactive sites in the hypothalamus. An updated model is presented to explain how the concurrent actions of aminergic neurotransmitters acting on their respective receptors in the hypothalamus can interact with a PGE to elicit hyperthermia. Finally, an evaluation of the current literature including recent findings on macrophage inflammatory protein (MIP-1) supports the conclusion that a PGE in the brain is neither an obligatory nor essential factor for the expression of a pyrogen fever.
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PMID:Prostaglandins and hypothalamic neurotransmitter receptors involved in hyperthermia: a critical evaluation. 790 92

Macrophage inflammatory protein-1 (MIP-1), a novel cytokine composed of alpha/beta subunits, is released from macrophages during infection. MIP-1 injected intravenously in the rabbit or into the anterior hypothalamic, preoptic area (AH/POA) of the rat causes an intense fever, which is not blocked by prostaglandin synthesis inhibitors, ibuprofin or indomethacin, respectively. The purpose of this study was to determine the role of de novo protein synthesis on the fever evoked by MIP-1 applied to thermosensitive cells of the AH/POA. Guide cannulae were implanted bilaterally above the AH/POA or ventral septal area (VSA) and medially above the third cerebral ventricle in each of 11 male Sprague-Dawley rats. Following postoperative recovery, body temperature (Tb) was monitored by a colonic thermistor probe. The bilateral microinjection of MIP-1 in a dose of 14 pg per 0.5 microliters into the AH/POA caused a biphasic elevation in Tb to 0.9 +/- 0.2 degrees C within 1.0 h, which reached 1.5 +/- 0.2 degrees C within 3.0 h, and persisted for over 6.0 h. An identical injection of MIP-1 into the VSA increased Tb biphasically to 0.1 +/- 0.1 degrees C within 1.0 h and to 0.8 +/- 0.3 degrees C within 3.0 h. The infusion into the third ventricle of 80 micrograms/10 microliters of the inhibitor of protein synthesis, anisomycin, either 10 or 30 min before the microinjection of MIP-1 into the AH/POA, attenuated significantly the rise in Tb for 1.0 to 3.0 h or 2.5 to 3.0 h, respectively. These results coincide with the earlier finding that anisomycin inhibits both endotoxin- and IL-1 beta-induced fevers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever evoked by macrophage inflammatory protein-1 (MIP-1) injected into preoptic or ventral septal area of rats depends on intermediary protein synthesis. 831 99

Changes in body temperature (Tb) and feeding were characterized in unrestrained rats following the micro-injection into the anterior hypothalamic preoptic area (AH/POA) of macrophage inflammatory protein-1 (MIP-1), MIP-1 alpha or MIP-1 beta. After the rats recovered from the stereotaxic implantation of a single guide tube placed in the AH/POA, either one of the MIP-1 compounds or control CSF was micro-injected in a volume of 1.0 microliter into this area. Changes in body temperature (Tb) and food and water intakes were monitored throughout each experiment. When micro-injected into the AH/POA in a dose of 28 or 280 pg, doublet MIP-1 and MIP-1 beta evoked a monophasic fever which increased above baseline to a mean maximum of 2.17 +/- 0.14 degrees C and 2.1 +/- 0.24 degrees C, respectively. MIP-1 alpha micro-injected similarly evoked a biphasic fever, with the Tb declining transiently at the 30 min point > or = 0.4 degrees C lower than the congruent rises in Tb evoked by doublet MIP-1 or MIP-1 beta. The secondary rise in Tb induced by MIP-1 alpha had a latency of 1.5-2.0 hrs and reached a maximum of 1.56 +/- 0.16 degrees C. Although all three cytokines significantly attenuated the rats' mean intake of food during the 24 hr interval after their micro-injection into the AH/POA, doublet MIP-1 exerted the most potent anorexic effect in comparison to that of the saline control rats. However, neither body weight nor intake of water was altered significantly by the three cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever and feeding: differential actions of macrophage inflammatory protein-1 (MIP-1), MIP-1 alpha and MIP-1 beta on rat hypothalamus. 851 Jul 94

The effect of macrophage inflammatory protein-1 beta (MIP-1 beta) on body temperature, following its injection into the anterior hypothalamic pre-optic area (AH/POA), was examined by a radiotelemetry system in the freely moving rat. The purpose of this study was to examine the action of an inhibitor of protein synthesis, anisomycin, on the pyrexia which follows intrahypothalamic injection of MIP-1 beta. The micro-injection of 10 to 20 pg MIP-1 beta into the AH/POA induced a dose-dependent monophasic increase in body temperature, whereas a higher dose of 25 pg of the cytokine caused a biphasic febrile response. When MIP-1 beta was heated at 70 degrees C for 30 min prior to its administration, the pyrogenic response was abolished. Pretreatment of the micro-injection site in the AH/POA with 10 micrograms anisomycin did not alter the febrile response to 25 pg MIP-1 beta given at the same site in the AH/POA. When 10 mg/kg anisomycin was administered subcutaneously, the febrile response to 25 pg MIP-1 beta injected in the AH/POA was significantly suppressed. The present results suggest that fever caused by MIP-1 beta within the cells of the AH/POA may not require the synthesis of a new protein factor; however, the de novo synthesis of a protein outside of the AH/POA presumably plays a functional role, at least in part, in the intense fever produced by this cytokine in the hypothalamus.
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PMID:Fever induced in rats by intrahypothalamic macrophage inflammatory protein (MIP)-1 beta: role of protein synthesis. 858 2

The purpose of this study was to investigate the role of pyrogenic cytokines, such as IL-1 beta, IL-6 and MIP-1 beta, in the mechanisms underlying the hyperthermic response of rats to central injection of PGE2. Thus, specific murine neutralizing antibodies against these cytokines were micro-injected directly into the anterior hypothalamic, preoptic area (AH/POA) of unrestrained rats just before intracerebroventricular injection of PGE2. The significant hyperthermia induced by PGE2 was markedly suppressed by micro-injection of anti-IL-6 and partially attenuated by anti-IL-1 beta. However, the micro-injection of anti-MIP-1 beta failed to alter the hyperthermic response. The results indicate that PGE2-induced hyperthermia is presumably mediated through actions of IL-6 on the thermosensitive cells of the AH/POA and confirm that distinct and alternate pathways exist in the rat brain for the induction of fever.
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PMID:Role of interleukin-1 beta, interleukin-6 and macrophage inflammatory protein-1 beta in prostaglandin-E2-induced hyperthermia in rats. 880 17


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