AUTHOR=Niu Hui , Yang Tianli , Wang Jin , Wang Rui , Cai Yun
TITLE=Immunomodulatory Effect of Colistin and its Protective Role in Rats with Methicillin-Resistant Staphylococcus aureus-induced Pneumonia
JOURNAL=Frontiers in Pharmacology
VOLUME=11
YEAR=2021
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.602054
DOI=10.3389/fphar.2020.602054
ISSN=1663-9812
ABSTRACT=Objectives: Colistin is the last resort of antimicrobials against multi-drug resistant Gram-negative pathogens. Previous studies in Caenorhabditis elegans and macrophages of rats have suggested that colistin possesses the immunomodulatory properties by acting p38/MAPK pathway. Here, we aimed to confirm the immunomodulatory role of colistin in animal models.
Methods: Rat model of Methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia was established. Plasma concentrations of proinflammatory cytokines, quantitative bacteriology, histology and immunohistochemistry of lungs were assessed to compare the immunomodulatory properties of colistin pre-administration.
Results: The numbers of white blood cells and granulocytes were significantly increased in the 9 mg/kg colistin pre-administration group at 72 h after infection. Levels of TNF-α, IL-6 and IL-1β in plasma after colistin pre-administration were lower compared with the infected group without treatment. Colistin pre-treatment resulted in lower bacterial counts, a dramatic decrease of cytokines and improved histopathological injury in infected lung tissues compared with the untreated animals. However, p38/MAPK inhibitor SB203580 did not fully block the above-mentioned effects caused by colistin.
Conclusion: Pre-administration of colistin could attenuate an excessive inflammatory reaction and protect the lungs from MRSA-associated damages. However, these effects could not be reversed by blocking the p38/MAPK pathway alone. Collectively, the mechanism underlying the immunoregulatory effects of colistin in mammals needs to be further explored.