Endotoxin-induced cytokine gene expression in vivo: IV. Expression of interleukin-1α/β and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation

T. R. Ulich, K. Guo, S. Yin, J. Del Castillo, E. S. Yi, R. C. Thompson, S. P. Eisenberg

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1α/β (IL-1α/β) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL- 1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalAmerican Journal of Pathology
Volume141
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

Endotoxemia
Interleukin-1 Receptors
Interleukin-1
Endotoxins
Lipopolysaccharides
Cytokines
Inflammation
Gene Expression
Messenger RNA
Bronchoalveolar Lavage
Lung
Injections
Interleukin 1 Receptor Antagonist Protein
Intravenous Injections
Neutrophils
Down-Regulation
RNA
Alveolar Macrophages
Pneumonia
Up-Regulation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Endotoxin-induced cytokine gene expression in vivo : IV. Expression of interleukin-1α/β and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation. / Ulich, T. R.; Guo, K.; Yin, S.; Del Castillo, J.; Yi, E. S.; Thompson, R. C.; Eisenberg, S. P.

In: American Journal of Pathology, Vol. 141, No. 1, 1992, p. 61-68.

Research output: Contribution to journalArticle

@article{197613673514461a96c87879166f441c,
title = "Endotoxin-induced cytokine gene expression in vivo: IV. Expression of interleukin-1α/β and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation",
abstract = "After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1α/β (IL-1α/β) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95{\%} PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL- 1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.",
author = "Ulich, {T. R.} and K. Guo and S. Yin and {Del Castillo}, J. and Yi, {E. S.} and Thompson, {R. C.} and Eisenberg, {S. P.}",
year = "1992",
language = "English (US)",
volume = "141",
pages = "61--68",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Endotoxin-induced cytokine gene expression in vivo

T2 - IV. Expression of interleukin-1α/β and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation

AU - Ulich, T. R.

AU - Guo, K.

AU - Yin, S.

AU - Del Castillo, J.

AU - Yi, E. S.

AU - Thompson, R. C.

AU - Eisenberg, S. P.

PY - 1992

Y1 - 1992

N2 - After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1α/β (IL-1α/β) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL- 1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.

AB - After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1α/β (IL-1α/β) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL- 1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.

UR - http://www.scopus.com/inward/record.url?scp=0026720502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026720502&partnerID=8YFLogxK

M3 - Article

C2 - 1385928

AN - SCOPUS:0026720502

VL - 141

SP - 61

EP - 68

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -