Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages

Patients with severe burn injuries are extremely susceptible to infection, and the host's antibacterial responses are frequently suppressed by alternatively activated macrophages (M2M phi), commonly demonstrated in these patients. An immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral blood of thermally injured patients, has been described as an inducer of M2M phi. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2M phi generation stimulated by PMN-II was examined. M2M phi were generated from resident M phi (R-M phi, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2M phi were not generated from R-M phi when the same transwell cultures were performed in the presence of GL. M2M phi were not generated from R-M phi after cultivation with PMN-II previously treated with GL, while R-M phi previously treated with GL converted to M2M phi after they were cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II were shown to be effector molecules responsible for the generation of M2M phi. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2M phi generation through the inhibition of CCL2/interleukin-10 production by PMN-II. (c) 2006 Elsevier Ltd. All rights reserved.