Distribution and chemotactic mechanism of CD4+ T cells in traumatic tracheal stenosis.

A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4+ T lymphocytes being the predominant immune cells in TS, the mechanism of action and recruitment has not been described. In our research, using flow cytometry, ELISA, immunofluorescence, and Transwell chamber assays, the expression, distribution, and potential chemotactic function of CD4+ T cells in TS patients were examined before and after treatment. The results showed that the untreated group had significantly more CD4+ T cells and their secreted TGF-ß1 than the treated group. Additionally, the untreated group's CD4+ T cells showed a significant rise in CCL22 and CCL1, as well as a larger proportion of CCR4 and CCR8. CD4+ T cells and CD68+ macrophages located in TS also expressed CCL1 and CCL22. In vitro, anti-CCL1 and anti-CCL22 can partially block the chemoattractant effect of TS bronchoalveolar lavage (BAL) on purified CD4+ T cells. The findings of this study indicated that TS contained unbalanced CD4 immune cells that were actively recruited locally by CCR4/CCL22 and CCR8/CCL1. As a result, it is anticipated that CD4 immune rebalancing can serve as a novel treatment for TS.

Erythromycin combined with corticosteroid reduced inflammation and modified trauma-induced tracheal stenosis in a rabbit model.

BACKGROUND: Patients with endotracheal intubation or tracheostomy are subject to benign tracheal stenosis (TS), for which current therapies are unsatisfactory. We conducted a preliminary investigation of drugs and drug combinations for the prevention and treatment of TS in a rabbit model. METHODS: Fifty-four rabbits were apportioned into nine groups according to treatment: sham-operated control; untreated TS model; amikacin; budesonide; erythromycin; penicillin; amikacin + budesonide; erythromycin + budesonide; and penicillin + budesonide. TS was induced by abrasion during surgery. The drugs were applied for 7 days before and 10 days after the surgery. Rabbits were killed on the eleventh day. Tracheal specimens were processed for determining alterations in the thicknesses of tracheal epithelium and lamina propria via hematoxylin and eosin. The tracheal mRNA (assessed by real-time quantitative polymerase chain reaction) expressions of the following fibrotic-related factors were determined: transforming growth factor-ß1 (TGF- ß1), collagen type I (COL1A1), collagen type III (COL3A1), and interleukin-17 (IL-17). The protein levels of TGF-ß1, COL1A1, and COL3A1 were determined through immunohistochemistry and integrated optical densities. RESULTS: Compared with all other groups, the untreated TS model had significantly thicker tracheal epithelium and lamina propria, and higher mRNA and protein levels of all targeted fibrotic factors. The mRNA and protein levels of the targeted fibrotic factors in all the drug-treated groups were lower than those of the untreated TS model, and differences were most significant in the erythromycin + budesonide group. CONCLUSIONS: Erythromycin combined with budesonide may reduce inflammation and modify fibrosis progression in TS after tracheal injury.