A mechanism of interleukin-12 unresponsiveness associated with thermal injury

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

Research output: Contribution to journalArticle

18 Scopus citations

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
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

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