A mechanism of interleukin-12 unresponsiveness associated with thermal injury

Tokuichiro Utsunomiya, Makiko Kobayashi, David Herndon, Richard B. Pollard, Fujio Suzuki

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

An unresponsive state for the production of interleukin-12 (IL-12) is commonly observed in animals and patients with severe thermal injuries. In the present study, the participation of corticosteroids, prostaglandin E2 (PGE2), and type 2 cytokines, which appeared in association with thermal injury, on the burn-associated IL-12 unresponsiveness was studied. These substances have been described as inhibitors of IL-12 production. Less than 20 pg/ml serum IL-12 was produced in thermally injured mice (TI-mice) after stimulation with lipopolysaccharide (LPS), while 1037 pg/ml IL-12 was detected in sera of unburned mice equally stimulated with LPS. Almost complete restoration of the impaired IL-12 production was witnessed in TI-mice after treatment with soluble IL-4 receptor (50 ng/mouse, 2 h and 2 days after thermal injury). However, IL-12 was not induced by LPS stimulation in TI-mice treated with an inhibitor of PGE2 (indomethacin, 0.1-5 mg/kg) or an inhibitor of corticosteroid production (ketoconazole, 10 mg/kg). LPS-stimulated IL-12 production was also impaired in normal mice inoculated with burn-associated type 2 T cells. In addition, in the presence of 1 μg/ml LPS, naive macrophages cocultured with burn-associated type 2 T cells did not produce IL-12 in their culture fluids, while IL-12 was produced by LPS-stimulated naive macrophages that were cocultured with naive splenic CD8+ T cells. These results suggest that the IL-12-unresponsive state demonstrated in TI-mice is associated mainly with type 2 cytokines released from burn-associated type 2 T cells.

Original languageEnglish (US)
Pages (from-to)211-217
Number of pages7
JournalJournal of Surgical Research
Volume96
Issue number2
DOIs
StatePublished - 2001

Fingerprint

Interleukin-12
Hot Temperature
Wounds and Injuries
Lipopolysaccharides
Burns
T-Lymphocytes
Dinoprostone
Adrenal Cortex Hormones
Macrophages
Interleukin-4 Receptors
Cytokines
Ketoconazole
Serum
Indomethacin

ASJC Scopus subject areas

  • Surgery

Cite this

A mechanism of interleukin-12 unresponsiveness associated with thermal injury. / Utsunomiya, Tokuichiro; Kobayashi, Makiko; Herndon, David; Pollard, Richard B.; Suzuki, Fujio.

In: Journal of Surgical Research, Vol. 96, No. 2, 2001, p. 211-217.

Research output: Contribution to journalArticle

Utsunomiya, Tokuichiro ; Kobayashi, Makiko ; Herndon, David ; Pollard, Richard B. ; Suzuki, Fujio. / A mechanism of interleukin-12 unresponsiveness associated with thermal injury. In: Journal of Surgical Research. 2001 ; Vol. 96, No. 2. pp. 211-217.
@article{2ad0c835f66041db808923d035b67b34,
title = "A mechanism of interleukin-12 unresponsiveness associated with thermal injury",
abstract = "An unresponsive state for the production of interleukin-12 (IL-12) is commonly observed in animals and patients with severe thermal injuries. In the present study, the participation of corticosteroids, prostaglandin E2 (PGE2), and type 2 cytokines, which appeared in association with thermal injury, on the burn-associated IL-12 unresponsiveness was studied. These substances have been described as inhibitors of IL-12 production. Less than 20 pg/ml serum IL-12 was produced in thermally injured mice (TI-mice) after stimulation with lipopolysaccharide (LPS), while 1037 pg/ml IL-12 was detected in sera of unburned mice equally stimulated with LPS. Almost complete restoration of the impaired IL-12 production was witnessed in TI-mice after treatment with soluble IL-4 receptor (50 ng/mouse, 2 h and 2 days after thermal injury). However, IL-12 was not induced by LPS stimulation in TI-mice treated with an inhibitor of PGE2 (indomethacin, 0.1-5 mg/kg) or an inhibitor of corticosteroid production (ketoconazole, 10 mg/kg). LPS-stimulated IL-12 production was also impaired in normal mice inoculated with burn-associated type 2 T cells. In addition, in the presence of 1 μg/ml LPS, naive macrophages cocultured with burn-associated type 2 T cells did not produce IL-12 in their culture fluids, while IL-12 was produced by LPS-stimulated naive macrophages that were cocultured with naive splenic CD8+ T cells. These results suggest that the IL-12-unresponsive state demonstrated in TI-mice is associated mainly with type 2 cytokines released from burn-associated type 2 T cells.",
author = "Tokuichiro Utsunomiya and Makiko Kobayashi and David Herndon and Pollard, {Richard B.} and Fujio Suzuki",
year = "2001",
doi = "10.1006/jsre.2001.6088",
language = "English (US)",
volume = "96",
pages = "211--217",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - A mechanism of interleukin-12 unresponsiveness associated with thermal injury

AU - Utsunomiya, Tokuichiro

AU - Kobayashi, Makiko

AU - Herndon, David

AU - Pollard, Richard B.

AU - Suzuki, Fujio

PY - 2001

Y1 - 2001

N2 - An unresponsive state for the production of interleukin-12 (IL-12) is commonly observed in animals and patients with severe thermal injuries. In the present study, the participation of corticosteroids, prostaglandin E2 (PGE2), and type 2 cytokines, which appeared in association with thermal injury, on the burn-associated IL-12 unresponsiveness was studied. These substances have been described as inhibitors of IL-12 production. Less than 20 pg/ml serum IL-12 was produced in thermally injured mice (TI-mice) after stimulation with lipopolysaccharide (LPS), while 1037 pg/ml IL-12 was detected in sera of unburned mice equally stimulated with LPS. Almost complete restoration of the impaired IL-12 production was witnessed in TI-mice after treatment with soluble IL-4 receptor (50 ng/mouse, 2 h and 2 days after thermal injury). However, IL-12 was not induced by LPS stimulation in TI-mice treated with an inhibitor of PGE2 (indomethacin, 0.1-5 mg/kg) or an inhibitor of corticosteroid production (ketoconazole, 10 mg/kg). LPS-stimulated IL-12 production was also impaired in normal mice inoculated with burn-associated type 2 T cells. In addition, in the presence of 1 μg/ml LPS, naive macrophages cocultured with burn-associated type 2 T cells did not produce IL-12 in their culture fluids, while IL-12 was produced by LPS-stimulated naive macrophages that were cocultured with naive splenic CD8+ T cells. These results suggest that the IL-12-unresponsive state demonstrated in TI-mice is associated mainly with type 2 cytokines released from burn-associated type 2 T cells.

AB - An unresponsive state for the production of interleukin-12 (IL-12) is commonly observed in animals and patients with severe thermal injuries. In the present study, the participation of corticosteroids, prostaglandin E2 (PGE2), and type 2 cytokines, which appeared in association with thermal injury, on the burn-associated IL-12 unresponsiveness was studied. These substances have been described as inhibitors of IL-12 production. Less than 20 pg/ml serum IL-12 was produced in thermally injured mice (TI-mice) after stimulation with lipopolysaccharide (LPS), while 1037 pg/ml IL-12 was detected in sera of unburned mice equally stimulated with LPS. Almost complete restoration of the impaired IL-12 production was witnessed in TI-mice after treatment with soluble IL-4 receptor (50 ng/mouse, 2 h and 2 days after thermal injury). However, IL-12 was not induced by LPS stimulation in TI-mice treated with an inhibitor of PGE2 (indomethacin, 0.1-5 mg/kg) or an inhibitor of corticosteroid production (ketoconazole, 10 mg/kg). LPS-stimulated IL-12 production was also impaired in normal mice inoculated with burn-associated type 2 T cells. In addition, in the presence of 1 μg/ml LPS, naive macrophages cocultured with burn-associated type 2 T cells did not produce IL-12 in their culture fluids, while IL-12 was produced by LPS-stimulated naive macrophages that were cocultured with naive splenic CD8+ T cells. These results suggest that the IL-12-unresponsive state demonstrated in TI-mice is associated mainly with type 2 cytokines released from burn-associated type 2 T cells.

UR - http://www.scopus.com/inward/record.url?scp=0035747105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035747105&partnerID=8YFLogxK

U2 - 10.1006/jsre.2001.6088

DO - 10.1006/jsre.2001.6088

M3 - Article

VL - 96

SP - 211

EP - 217

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -