Gastric cytoprotection by intracisternal interleukin-1β in the rat

doi:10.1016/0006-291X(91)91536-L

Biochemical and Biophysical Research Communications

Volume 174, Issue 3, 14 February 1991, Pages 1117-1124

https://doi.org/10.1016/0006-291X(91)91536-L Get rights and content

Abstract

The effects of intracisternal (ic) injection of recombinant interleukin-1β(IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The cytoprotective effect was dose dependent (ED₁₇₅ ng/rat), long lasting with a maximal action when given 1–3 h prior to ethanol, blocked by ic injection of a IL-1 receptor antagonist protein (IRAP), and by intraperitoneal injection of indomethacin. IL-1, injected ic, was detected in the peripheral blood. However, IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose giving equal gastric protection. These data show that ic IL-1 induces long lasting gastric protection mediated by interaction with IL-1 receptors and prostaglandin pathways at central and/or peripheral sites that remain to be localized.

References (35)

J.J. Oppenheim et al.
Immunol. Today
(1986)
G. Katsuura et al.
Biochem. Biophys. Res. Comm
(1988)
N. Murakami et al.
Brain Res
(1989)
T. Nakashima et al.
Brain Res. Bull
(1989)
E. Saperas et al.
Gastroenterology
(1990)
Y. Taché et al.
Gastroenterology
(1988)
Y. Taché et al.
Life Sc
(1979)
A. Robert et al.
Gastroenterology
(1979)
J.L. Wallace et al.
Eur. J. Pharmacol
(1990)
A. Robert et al.
Life Sc
(1991)

T. Okumura et al.

Biochem. Biophys. Res. Comm

(1990)

C.V. Grijalva et al.

Brain Res. Bull

(1980)

F. Cominelli et al.

Gastroenterology

(1989)

C.A. Dinarello

FASEB J

(1988)

W.L. Farrar et al.

J. Immunol

(1987)

C.D. Breder et al.

Science

(1988)

N.J. Rothwell

Am. J. Physiol

(1989)

Cited by (26)

No association between IL-1RN VNTR and the risk of duodenal ulcer: A meta-analysis
2013, Human Immunology
Citation Excerpt :
Recently, evidence-based studies demonstrated that IL-1RN VNTR was associated with various diseases [55,56]. With respect to DU, a variety of studies have focused on the association of IL-1RN VNTR as IL-1ra can exert important influence on IL-1β levels, which has been reported to be a gastric cytoprotective molecule and can be up-regulated by H. pylori infection [5,6,57,58]. However, the observed associations of these studies were inconclusive.
The aim of this study was to perform a meta-analysis to investigate a more authentic association between interleukin-1 RN variable number of tandem repeats (IL-1RN VNTR) and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 16 studies including 2115 cases and 3622 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1RN VNTR and DU (allelic model: OR = 1.04, 95%CI = 0.87–1.26; additive model: OR = 0.85, 95%CI = 0.62–1.16; dominant model: OR = 1.06, 95%CI = 0.92–1.23; and recessive model: OR = 0.83, 95%CI = 0.61–1.12). Significant protective associations were found in additive model (OR = 0.51, 95%CI = 0.31–0.83) and recessive model (OR = 0.45, 95%CI = 0.28–0.73) in Caucasian subgroup. In conclusion, our meta-analysis suggests that there is no evidence of significant association between IL-1RN VNTR and DU with or without Helicobacter pylori infection in overall population, whereas significant association is found by subgroup analyses which showed protective effect of IL-1RN allele 2 against DU risk in Caucasian population.
No association between IL-1β -31 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 3793 subjects
2012, Human Immunology
Citation Excerpt :
Also there was no evidence of publication bias among studies in all genetic models using Egger’s regression test (P = 0.95 for allelic model, P = 0.73 for additive model, P = 0.49 for dominant model, P = 0.08 for recessive model, respectively). IL-1β has been reported to be a gastric cytoprotective molecule and can be up-regulated by H. pylori infection [5–7,34–36]. Precisely because of the significant role of IL-1β in the regulation of acid secretion and cytoprotection of the gastrointestinal mucosa, to date, many studies have evaluated the association between IL-1β −31 C/T polymorphism and DU risk, but the results remain inconsistent.
The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β −31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β −31 C/T polymorphism and DU (allelic model: OR = 0.96, 95%CI = 0.86–1.07; additive model: OR = 0.85, 95%CI = 0.67–1.07; dominant model: OR = 0.95, 95%CI = 0.81–1.13; and recessive model: OR = 0.95, 95%CI = 0.79–1.15). Significant association was found in additive model for PB subgroup (OR = 0.65, 95%CI = 0.44–0.96) and recessive model for non-Asian subgroup (OR = 0.72, 95%CI = 0.52–0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β −31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.
No association between IL-1β -511 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 4667 subjects
2012, Gene
Citation Excerpt :
Also there was no evidence of publication bias among studies in all genetic models using Egger's regression test (P = 0.93 for T vs. C, P = 0.86 for TT vs. CC, P = 0.73 for the dominant model, P = 0.50 for the recessive model, respectively). IL-1β is up-regulated by H. pylori infection and is involved in reducing gastric damage induced by a variety of ulcerogenic agents (Lindholm et al., 1998; Noach et al., 1994; Robert et al., 1991a, 1991b). Precisely because of the significant role of IL-1β in the regulation of acid secretion and cytoprotection of the gastrointestinal mucosa, to date, many studies have evaluated the association between IL-1β − 511 C/T polymorphism and DU risk, but the results remain controversial and call for further assessment.
Epidemiological studies have evaluated the association between IL-1β − 511 C/T polymorphism and duodenal ulcer (DU) risk. However, the results remain conflicting. The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β − 511 C/T polymorphism and DU. Systematic searches of electronic databases Embase, PubMed and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 14 studies including 1887 cases and 2780 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β − 511 C/T polymorphism and DU (for T allele vs. C allele: OR = 0.93, 95% CI = 0.82–1.06; for T/T vs. C/C: OR = 0.83, 95% CI = 0.64–1.08; for dominant model: OR = 0.93, 95% CI = 0.80–1.07; and for recessive model: OR = 0.87, 95% CI = 0.69–1.11). Significant association was found in all genetic models for the PB subgroup and sensitivity analyses. In conclusion, our meta-analysis suggests that there was no evidence of a significant association between IL-1β − 511 C/T polymorphism and DU with or without Helicobacter pylori infection, whereas a significant association was found by sensitivity analyses which showed a protective effect of the T allele against DU risk.
Effects of IL-1β on neuronal activities in the dorsal motor nucleus of the vagus in rat brain slices
1996, Brain Research Bulletin
Effects of recombinant human interleukin-1β (IL-1β) on the neuronal activities in the rat dorsal motor nucleus of the vagus (DMV) were investigated by extra- and intracellular recordings in slice preparations. Twelve (52%) of 23 spontaneously firing neurons recorded extracellularly, 7 of which were electrophysiologically identified as vagal motoneurons, were inhibited by a bath application of IL-1β at a dose of either 5.8 × 10⁻⁸ or 5.8 × 10⁻⁹ M. The duration of the responses ranged widely from about 10 min to more than 2 h. Two (9%) of the 23 neurons were excited, whereas the remaining 9 (39%) were not affected by IL-1β. Of 42 DMV neurons recorded intracellularly, 19 (45%) showed a hyperpolarization following an application of 5.8 × 10⁻⁸ M IL-1β, which still persisted in a TTX-containing solution. Two (5%) displayed depolarization and 21 (50%) were unaffected. The hyperpolarization in 16 of the 19 neurons (84%) ranged from −5 to −10 mV and lasted for more than 30 min without changing the input resistance. The IL-1β-induced hyperpolarization was completely blocked by concurrent perfusion with sodium salicylate. The remaining three neurons showed a short-lasting (5–14 min) hyperpolarization (ranging from −6 to −15 mV) with a decrease in the input resistance. These findings indicate that IL-1β mainly inhibits the vagal motoneurons in the DMV, at least partly through prostaglandin synthesis. This provides a mechanism that could account for the central action of IL-1β on visceral processes such as the inhibition of gastric acid secretion.
Interleukin 1β inhibits gastric emptying in rats: Mediation through prostaglandin and corticotropin-releasing factor
1994, Gastroenterology
Background/Aims: Interleukin 1β (IL-1β) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1β on gastric emptying were investigated. Methods: The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1β in conscious rats. Results: IL-1β injected intracisternally (0.01–1 ng) or intravenously (0.01–10 ng) dose-dependently decreased gastric emptying by 10%–82% and 0%–89%, respectively. The median effective dose (ED₅₀) was 30-fold lower when IL-1β was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1β had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1β (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe¹², Nle^21,38,C^αMeLeu³⁷]CRF_12–41 (20 μg) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1β (0.1 ng). The antagonists alone had no effect on basal gastric emptying. Conclusions: IL-1β acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1β action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.
The effect of interleukin 1α on acetaminophen-induced hepatotoxicity
1993, Cytokine
The protective effect of interleukin 1α (IL-1α) in mice with acetaminophen (AAP)-induced hepatitis was investigated. IL-1α had a significant protective effect if given 2 or more hours (up to 24 hours) before AAP; it significantly reduced mortality of mice and decreased serum transaminase level. The maximal effect was obtained with the dose of 1000 U (166 mg/kg) IL-1α. Pretreatment with IL-1 significantly increased the synthesis of prostaglandin E₂ (PGE₂) in samples of liver tissue from AAP-treated mice, but had no effect on the synthesis of leukotriene C₄ (LTC₄). Pretreatment with indomethacin (IMC) did not abrogate significantly the protective effect of IL-1. Thus, the hepatoprotective effect of IL-1α can not be entirely explained by the stimulation of prostaglandin (PG) synthesis.

View all citing articles on Scopus

View full text

Gastric cytoprotection by intracisternal interleukin-1β in the rat

Abstract

Immunol. Today

Biochem. Biophys. Res. Comm

Brain Res

Brain Res. Bull

Gastroenterology

Gastroenterology

Life Sc

Gastroenterology

Eur. J. Pharmacol

Life Sc

Biochem. Biophys. Res. Comm

Brain Res. Bull

Gastroenterology

FASEB J

J. Immunol

Science

Am. J. Physiol