Glycyrrhizin restores the impaired IL-12 production in thermally injured mice

Mice 6 days after thermal injury (TI-mice) did not respond to lipopolysacch aride (LPS) stimulation for production of serum interleukin 12 (IL-12; 2 h after LPS stimulation, < 20 pg/ml in TI-mice; 1091 +/- 162pg/ml in normal m ice). However, 2h after LPS stimulation, 1456 +/- 118 pg/ml of IL-12 were d emonstrated in sera of TI-mice previously treated with a 10 mg/kg i.p. dose of glycyrrhizin (GR), IL-12 was not induced by LPS in sera of normal mice inoculated with burn-associated type 2 T cells (IL-4/IL-10-producing CD8(+) CD11b(+) TCR gamma/delta (+) T cells isolated from spleens of TI-mice), Ho wever, IL-12 production was induced by LPS in sera of these mice previously treated with GR or a mixture of monoclonal antibodies (mAbs) for type 2 cy tokines, Also, IL-12 production was induced by LPS in TI-mice inoculated wi th CD4(+) T cells from spleens of GR-treated normal mice (GR-CD4(+) T cells , 5 x 10(6) cells/mouse), Since GR-CD4(+) T cells have been shown to be ant agonistic cells against production of type 2 cytokines by burn-associated t ype 2 T cells, these results indicate that IL-12 unresponsiveness shown in TI-mice is recovered by GR through the regulation of burn-associated type 2 -T cell responses. (C) 2001 Academic Press.