Intervention Effect Of Inflammatory Response By Synthetic TREM-1 Peptide During Pleural Empyema In Rats

Objective Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell-surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis and pneumonia. The aim of the present study was to investigate the intervention effect of inflammatory response by an analogue artificial synthetic peptide derived from the extracellular moiety of TREM-1 (LP-17) during experimental pleural empyema in rats.Methods Adult male Wistar rats were intrapleural inoculated with Pseudomonas aeruginosa (PAO1 strain) and Staphylococcus aureus (ATCC 25923), randomly treated or not treated with LP-17. We randomly selected rats in empyema group (n = 24), control group (n = 24), and LP17 group (n = 24) were sacrificed in group on 6 h, 12 h, 18 h, 24 h time points, at every time point, each group offer 6 rats to sacrificed. The thorax was opened and the amount of pleural effusion was recorded and analysed, and histopathology of pleura tissues were observed. Pleural fluid and serum was analyzed for the levels of IL-1β. In addition, a different set of rats was used to assess survival rate of 8 days: control group (n = 20), LP17 group (n = 20) and sham group (n = 20).Results P. aeruginosa and S. aureus induced a severe pleural empyema the first 24 h. LP17 reduced the total pleural effusion cell number and neutrophils number, compared with the control group and empyema group at 18 h and 24 h time points( P < 0.05 ). In comparison of IL-1βin pleural effusions, there was a statistical significance between LP-17 and control group, empyema group at time point 18 h, 24 h (P < 0.05). No impairment of CR3 expression in pleural effusion cells by LP17 treatment (P > 0.05). Histopathological examination of the visceral pleura and parietal pleura 24 h after P. aeruginosa and S. aureus instillation showed that leukocyte infiltration into the pleural space and edematous thickening of superfacial pleura were attenuated in the LP17-treated rats. Rats (n = 20 in each group) were monitored during 8 days after P. aeruginosa and S. aureus instillation. The survival rate was 15% in the control group, compared with 40% in LP17-treated rats (the LP17 group) (P < 0.05). No deaths were observed in the sham group.Conclusions In pleural empyema rats, LP17 improved hemodynamic status, modulated pleural and systemic inflammatory responses, reduced pleura histological damage, and improved survival. The modulation of the TREM-1 pathway by the use of such synthetic peptides as LP-17 appears beneficial during P. aeruginosa and S. aureus pleural empyema in rats in attenuating lung and systemic inflammatory responses.