Hypothalamic neuronal histamine modulates physiological responses induced by interleukin-1 beta

1995 ◽  
Vol 269 (6) ◽  
pp. R1308-R1313 ◽  
Author(s):  
M. Kang ◽  
H. Yoshimatsu ◽  
S. Chiba ◽  
M. Kurokawa ◽  
R. Ogawa ◽  
...  
Keyword(s):  
Body Temperature ◽  
Intraperitoneal Injection ◽  
Histidine Decarboxylase ◽  
Interleukin 1 ◽  
Suppressive Effect ◽  
Ingestive Behavior ◽  
Interleukin 1 Beta ◽  
Hypothalamic Histamine ◽  
Food And Water Intake ◽  
Neuronal Histamine

Dynamic involvement of hypothalamic histamine in ingestive behavior and thermogenesis induced by interleukin-1 beta (IL-1 beta) was examined in rats. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta decreased food and water intake and elevated body temperature. However, depletion of neuronal histamine induced by intraperitoneal injection of 160 mumol/rat alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the suppressive effect on drinking, and enhanced the elevating effect on rectal temperature. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta increased hypothalamic histamine turnover rate. The same dose of IL-1 beta also increased activity of HDC and histamine-N-methyltransferase (HMT). These results suggest that IL-1 beta may stimulate synthesis and release of hypothalamic histamine in presynaptic terminals by activation of HDC and facilitate degradation of extracellular histamine by activation of MHT. These changes in the dynamics of hypothalamic histamine modulate IL-1 beta-induced ingestive behavior and body temperature.

Interleukin-1 beta causes the increase in anterior hypothalamic interleukin-6 during LPS-induced fever in rats

1994 ◽  
Vol 266 (6) ◽  
pp. R1845-R1848 ◽  
Author(s):  
J. J. Klir ◽  
J. L. McClellan ◽  
M. J. Kluger
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Temperature ◽  
Interleukin 6 ◽  
Intraperitoneal Injection ◽  
Core Body Temperature ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Time Points ◽  
Core Body ◽  
The Brain

The purpose of this study was to determine, using push-pull perfusion, whether the central pyrogenic action of interleukin-6 (IL-6) during lipopolysaccharide (LPS)-induced fever in rats is induced by interleukin-1 beta (IL-1 beta) and to determine the source of the hypothalamic IL-6 (i.e., from the periphery or from the brain). Samples of cerebrospinal fluid were collected 60 min before and 60, 120, 180, and 240 min after the intraperitoneal injection of LPS or saline as a control. Immediately before the injection of LPS, anti-rat neutralizing IL-1 beta antibody (anti-IL-1 beta) or control immunoglobulin G antibody (IgG) was microinjected into the anterior hypothalamus (AH) of each rat. At the end of the last perfusion, blood was collected by cardiac puncture. Microinjection of anti-IL-1 beta into the AH caused a 58% reduction of LPS fever (measured by biotelemetry). AH microinjection of anti-IL-1 beta or IgG followed by intraperitoneal injection of saline did not result in significant change in core body temperature. AH injection of anti-IL-1 beta also resulted in a 97% reduction in AH IL-6 levels during LPS fever, with the average values of IL-6 for the four post-LPS time points being 113 +/- 50 U/ml for the rats injected with IgG and LPS and 3 +/- 2 U/ml for the rats injected with anti-IL-1 beta and LPS (P = 0.024).(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of interleukin 1 beta and tumor necrosis factor in lipopolysaccharide fever in rats

1990 ◽  
Vol 259 (4) ◽  
pp. R724-R728 ◽  
Author(s):  
N. C. Long ◽  
I. Otterness ◽  
S. L. Kunkel ◽  
A. J. Vander ◽  
M. J. Kluger
Keyword(s):  
Tumor Necrosis Factor ◽  
Intravenous Injection ◽  
Intraperitoneal Injection ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Control Serum ◽  
Factor Alpha ◽  
Necrosis Factor

The roles of interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF) in lipopolysaccharide (LPS)-induced fever were investigated in the rat. We used antisera against IL-1 beta and TNF to determine whether we could alter the fever by blocking the action of these cytokines. The intravenous injection of antiserum IL-1 beta 3.5 days before the intraperitoneal injection of LPS resulted in a mean fever that was significantly lower than that seen in rats that had been injected with control serum (0.36 +/- 0.11 vs. 0.82 +/- 0.16 degrees C, P = 0.016). The intravenous injection of antiserum against TNF 3.5 days before the intraperitoneal injection of LPS did not block the fever but significantly enhanced it (1.31 +/- 0.16 vs. 0.82 +/- 0.16 degrees C, P = 0.027). These data support the hypotheses that IL-1 beta is responsible for a significant part of LPS fever and that TNF acts as an endogenous antipyretic to limit the magnitude of LPS fever in the rat.

Interleukin-8 induces fever by a prostaglandin-independent mechanism

1994 ◽  
Vol 266 (5) ◽  
pp. R1670-R1674 ◽  
Author(s):  
A. R. Zampronio ◽  
G. E. Souza ◽  
C. A. Silva ◽  
F. Q. Cunha ◽  
S. H. Ferreira
Keyword(s):  
Body Temperature ◽  
Interleukin 1 ◽  
Interleukin 8 ◽  
Cyclooxygenase Inhibitors ◽  
Interleukin 1 Beta ◽  
Independent Mechanism ◽  
Intracerebroventricular Injections ◽  
Beta 2 ◽  
Dose Dependent ◽  
Pyrogenic Activity

We have studied the mechanism by which interleukin-8 (IL-8) induces fever in rats. Intracerebroventricular injections of IL-8 (5.5-50 ng) evoked dose-dependent increases in body temperature, which reached a plateau 5 h after injection, i.e., later than intracerebroventricular interleukin-1 beta (IL-1 beta; 2 h). The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS) because preincubation of IL-8 with a specific antibody or boiling the IL-8 for 30 min abolished its activity but not that of LPS; also, IL-8 but not LPS induced fever in LPS-tolerant rats. Indomethacin significantly reduced the pyrogenic effects of intracerebroventricular injections of LPS and IL-1 beta but not responses to IL-8, suggesting that pyrogenic responses to IL-8 were mediated independently of prostaglandins. In contrast, dexamethasone markedly attenuated pyrogenic responses to IL-8 and IL-1 beta. These data suggest that inhibition of IL-8 by glucocorticoids contributes to the antipyretic effects of these drugs in fevers resistant to cyclooxygenase inhibitors.

Inhibitors of cytochrome P-450 augment fever induced by interleukin-1 beta

1996 ◽  
Vol 271 (5) ◽  
pp. R1274-R1279 ◽  
Author(s):  
T. Nakashima ◽  
Y. Harada ◽  
S. Miyata ◽  
T. Kiyohara
Keyword(s):  
Arachidonic Acid ◽  
Body Temperature ◽  
Preoptic Area ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Plateau Phase ◽  
Arachidonic Acid Cascade ◽  
Normal Body Temperature ◽  
Colonic Temperature ◽  
Cytochrome P 450

Metabolites of cytochrome P-450 are produced in cells when arachidonic acid cascade is activated. Fever genesis depends largely on the cyclooxygenase branch of arachidonic acid cascade, which is caused by many stimuli, such as interleukin (IL)-1, IL-6, and interferon-alpha. To assess the significance of cytochrome P-450 branch in fever, murine recombinant IL-1 beta was bilaterally microinjected (1 ng/microliter) into the medial preoptic area and anterior hypothalamus in conscious rats treated 60 min previously with or without the cytochrome P-450 inhibitor econazole (15 mg/kg im). The IL-1 beta-induced rise in colonic temperature was enhanced after the plateau phase of fever (from 240 min after IL-1 beta) in econazole-pretreated rats (P < 0.001). Another cytochrome P-450 inhibitor, clotrimazole (15 mg/kg im), also enhanced IL-1 beta-induced fever from 160 min after IL-1 beta injection (P < 0.001). Econazole also enhanced the fever when it was given 120 min before injection of IL-1 beta (P < 0.001). The cytochrome P-450 inhibitor, however, did not affect the fever when given 10 min after IL-1 beta (P = 0.95). Econazole and clotrimazole did not alter normal body temperature (P = 0.65 and 0.73, respectively). The results suggest that the metabolite(s) of cytochrome P-450 affect the falling phase after the plateau phase of fever and act as putative endogenous antipyretic(s).

Interleukin-1 beta inhibits gastric histamine secretion and synthesis in the rat

1994 ◽  
Vol 267 (6) ◽  
pp. G966-G971 ◽  
Author(s):  
S. Kondo ◽  
Y. Shinomura ◽  
S. Kanayama ◽  
S. Kawabata ◽  
Y. Miyazaki ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Histidine Decarboxylase ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Inhibitory Effects ◽  
Histamine Secretion ◽  
Basal Acid ◽  
Urinary Histamine

Interleukin-1 beta (IL-1 beta) is the most potent inhibitor of gastric acid secretion known at present. Although histamine has been shown to be an important mediator of gastric acid secretion, the effect of IL-1 beta on gastric histamine mobilization has not been studied. In the present study, the effects of IL-1 beta on gastric acid secretion and gastric histamine mobilization were investigated in conscious rats with both gastric and vesical fistulas. IL-1 beta (5 micrograms/kg iv) significantly inhibited basal acid secretion but did not affect basal urinary histamine excretion and fundic histidine decarboxylase (HDC) activity. Gastrin-17-I (1 nmol.kg-1.h-1) caused a marked increase in acid secretion, urinary histamine secretion, and fundic HDC activity. IL-1 beta (5 micrograms/kg iv) completely inhibited gastrin-induced acid secretion and partially inhibited urinary histamine excretion and fundic HDC activity. Pretreatment with indomethacin (10 mg/kg ip) partially reversed the inhibitory effects of IL-1 beta on gastrin-stimulated fundic HDC activity and acid secretion. These findings indicate that IL-1 beta inhibits gastric histamine mobilization through both prostaglandin-dependent and prostaglandin-independent pathways. Furthermore, it is suggested that the inhibitory action of IL-1 beta on gastric acid secretion is mediated by the inhibition of gastric histamine mobilization.

Effect of intravenous injection of IL-1 beta on PGE2 levels in several brain areas as determined by microdialysis

1992 ◽  
Vol 262 (2) ◽  
pp. E246-E251 ◽  
Author(s):  
G. Komaki ◽  
A. Arimura ◽  
K. Koves
Keyword(s):  
Intravenous Injection ◽  
Dorsal Hippocampus ◽  
Interleukin 1 ◽  
Suppressive Effect ◽  
Interleukin 1 Beta ◽  
Organum Vasculosum Laminae Terminalis ◽  
Pge2 Release ◽  
Before And After ◽  
A Site ◽  
The Brain

Using perfusion microdialysis, the effect of intravenous injection of recombinant human interleukin-1 beta (IL-1 beta) on prostaglandin E2 (PGE2) release into the interstitial fluid of the organum vasculosum laminae terminalis (OVLT), medial preoptic area (MPOA), paraventricular nucleus (PVN), dorsal hippocampus (HPC), and cerebrospinal fluid (CSF) of the lateral ventricle (LV) was examined. Artificial CSF was perfused through the dialysis probe and collected at 20-min intervals before and after IL-1 beta (1 microgram/100 g body wt iv). The results showed that 1) IL-1 beta induced a significant increase in PGE2 levels in the OVLT and the medial part of the MPOA in the first 20 min, which is more rapid and to a greater extent than that in PVN, HPC, and LV; 2) inclusion of indomethacin in the perfusate abolished the IL-1 beta-induced PGE2 response in the OVLT, but a suppressive effect in the PVN was insignificant. These results suggest that OVLT may be a gate for the entry of blood-borne IL-1 beta into the brain and a site where the initial biochemical response to IL-1 beta occurs.

CRF is involved in the pyrogenic and thermogenic effects of interleukin 1 beta in the rat

1989 ◽  
Vol 256 (1) ◽  
pp. E111-E115 ◽  
Author(s):  
N. J. Rothwell
Keyword(s):  
Body Temperature ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Interleukin 1 Beta ◽  
Blood Cell Count ◽  
Bat Activity

Interleukin 1 beta (IL-1 beta) is an endogenous peptide that induces fever, largely by central stimulation of sympathetically mediated thermogenesis. Microinjection (icv) of human recombinant IL-1 beta (50 ng) caused acute (response within 60 min) increases in colonic temperature (1.8 degrees C), oxygen consumption (Vo2; 36%), white blood cell count (96%), and brown adipose tissue (BAT) activity (mitochondrial GDP binding, 129%) in conscious rats. All of these effects were prevented or markedly inhibited by prior injection (icv) of an antagonist to corticotropin-releasing factor (CRF) [alpha-helical CRF-(9-41), 25 micrograms] and reduced by pretreatment with purified antibody to CRF. Injection of endotoxin (2 mg/kg ip), human recombinant tumor necrosis factor-alpha (TNF alpha; 5 micrograms icv) or prostaglandin E2 (PGE2; 100 ng icv) all stimulated body temperature (0.9-1.6 degrees C) and Vo2 (18-25%); TNF alpha did not affect white blood cell count but increased BAT activity by 38%. Prior injection of the CRF antagonist did not modify the actions of endotoxin, TNF alpha, or PGE2. Central injection of CRF (4 micrograms) produced a 23% increase in metabolic rate, which was unaffected by injection of the cycloxygenase inhibitor ibuprofen (5 mg/kg ip). These data indicate that the central effects of interleukin 1 beta on metabolic rate, body temperature, BAT activity, and white blood cell count are all mediated by release of CRF. The thermogenic effects of endotoxin, TNF alpha, and PGE2 are not dependent on CRF.

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