Glycyrrhizin restores the impaired IL-12 production in thermally injured mice.
Mice 6 days after thermal injury (TI-mice) did not respond to lipopolysaccharide (LPS) stimulation for production of serum interleukin 12 (IL-12; 2 h after LPS stimulation, <20 pg/ml in TI-mice; 1091+/-162 pg/ml in normal mice). However, 2 h after LPS stimulation, 1456+/-118 pg/ml of IL-12 were demonstrated 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+TCRgamma/delta+T cells isolated from spleens of TI-mice). However, 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 cytokines. Also, IL-12 production was induced by LPS in TI-mice inoculated with CD4+T cells from spleens of GR-treated normal mice (GR-CD4+T cells, 5x10(6)cells/mouse). Since GR-CD4+T cells have been shown to be antagonistic cells against production of type 2 cytokines by burn-associated type 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.
Utsunomiya
T
T
Department of Internal Medicine, The University of Texas Medical Branch, Gaveston 77555-0435, USA.
Kobayashi
M
M
Ito
M
M
Herndon
D N
DN
Pollard
R B
RB
Suzuki
F
F
D019264:Adoptive Transfer; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002056:Burns / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D019695:Glycyrrhizic Acid