Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis

Charles H. Lang, Jie Fan, Margaret M. Wojnar, Thomas C. Vary, Robert Cooney

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1β alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1β can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL- 1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1β (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1β. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1β is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume274
Issue number4 43-4
StatePublished - Apr 1 1998

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Endotoxemia
Insulin-Like Growth Factor I
Interleukin-1
Sepsis
Lipopolysaccharides
Interleukins
Peritonitis
Autocrine Communication
Paracrine Communication
Intraventricular Infusions
Kidney
Central Nervous System Infections
Injections
Interleukin-1 Receptors
Liver
Punctures
Endotoxins
Intravenous Administration
Growth Hormone
Intestines

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

@article{02527a6c21c64026a26440bd2b19c956,
title = "Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis",
abstract = "Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1β alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1β can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL- 1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1β (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36{\%} by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1β. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48{\%}, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35{\%}) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1β is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.",
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Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis. / Lang, Charles H.; Fan, Jie; Wojnar, Margaret M.; Vary, Thomas C.; Cooney, Robert.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 274, No. 4 43-4, 01.04.1998.

Research output: Contribution to journalArticle

TY - JOUR

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N2 - Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1β alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1β can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL- 1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1β (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1β. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1β is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.

AB - Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1β alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1β can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL- 1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1β (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1β. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1β is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.

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