A novel CXCL8-IP10 hybrid protein is effective in blocking pulmonary pathology in a mouse model of Klebsiella pneumoniae infection

作者:Chen, Zhangbo; Chen, Xiangyu; Cheng, Hsi-Tsung; Yeh, Shu-Chi; Yu, Hui-Yuan; Cheng, Jya-Wei*; Li, Fang*
来源:International Immunopharmacology, 2018, 62: 40-45.
DOI:10.1016/j.intimp.2018.06.040

摘要

Klebsiella pneumoniae (K. pneumoniae) is a hospital-acquired infectious agent that causes a range of diseases. Herein we have developed a novel CXCL8-IP10 hybrid protein and evaluated its efficacy in an animal model of K. pnewnoniae infection. Neutrophil chemotaxis data revealed that CXCL8-IP10 could inhibit human neutrophil chemotactic responses induced by the ELR-CXC chemokine CXCL8. To evaluate the effect of CXCL8-IPI0 on K. pnewnoniae infection, C57BL/6 mice were challenged with K. pnewnoniae followed by treatment with CXCL8-IP10 (500 pg/kg, i.p.), or dexamethasone (0.8 mg/kg, s.c.), or ceftazidime (200 mg/kg, s.c.) individually. CXCL8-IP10, dexamethasone or ceftazidime markedly inhibit Klebsiella-induced pulmonary inflammation as assessed by gross examination and histopathology. Moreover, the chemotactic responses of neutrophils was blocked by CXCL8-IP10 rather than dexamethasone or ceftazidime. Furthermore, the levels of inflammatory factors IL-1 beta, IFN-gamma and TNF-alpha were decreased after CXCL8-IP10, dexamethasone or ceftazidime treatment. Together, these results suggest that CXCL8-IP10 may provide a novel strategy for treating K. pneumoniae infection.

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