The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model

Background: The exact mechanism of the inflammatory changes occurring during the development of Behget's disease (BD) remains unclear. Objective: We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model. Methods: The classical vs. alternative activated macrophage ratio (Ml/M2 ratio) was calculated by analyzing the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow cytometry. mRNA expression of interferon (IFN)-gamma and interleukin (IL)-6 as M1 and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme-linked immunosorbent assay. Results: The M1 phenotype was upregulated in BD mice, and an increased M1/M2 ratio was observed compared to that in asymptomatic BD normal and normal healthy mice. Recombinant (r)IFN-gamma significantly increased the M1/M2 ratio (1.74 +/- 0.42) compared with that of rIL-4 (0.83 +/- 0.20). BD mice treated with rIL-4 showed a decreased Ml/M2 ratio (1.2 +/- 0.3) compared to that of the rIFN-gamma- (2.1 +/- 2.3) treated group and also showed ameliorated BD symptoms accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4. Conclusion: Therefore, modulation of macrophage phenotypes could be an effective therapeutic approach for treating BD in the future. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.