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New anti‐inflammatory benefits of antibiotics: Tulathromycin promotes apoptosis and efferocytosis, and inhibits pro‐inflammatory CXCL8 production in a model of porcine pleuropneumonia
Author(s) -
Duquette Stephanie,
Fischer Carrie D,
Muench Gregory P,
Lucas Merlyn J,
Buret Andre G
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb435
Subject(s) - efferocytosis , apoptosis , inflammation , pleuropneumonia , tunel assay , in vivo , immunology , interleukin 8 , medicine , microbiology and biotechnology , macrophage , chemistry , biology , in vitro , biochemistry
Neutrophil (PMN) apoptosis and subsequent clearance by surrounding macrophages (MΦ; efferocytosis) is critical to the resolution of inflammation following infection. Abnormal resolution of inflammation is responsible for the severe tissue damage characteristic of pneumonia, as in Actinobacillus pleuropneumoniae porcine pleuropneumonia. The superior clinical efficacy of some antibiotics has been attributed to inherent anti‐inflammatory properties via mechanisms that remain obscure. Objective to characterize anti‐inflammatory properties of tulathromycin (TUL) in a model of porcine pleuropneumonia. Results In vivo and in vitro , TUL induced porcine PMN apoptosis in a time‐and dose‐dependent manner, as determined by cell death ELISA, TUNEL fluorescent staining, and cleavage (activation) of caspase‐3, detected by western blot. TUL‐treated apoptotic PMN were readily efferocytosed by MΦ. TUL also induced delayed apoptosis and inhibited pro‐inflammatory CXCL8 production in porcine MΦ. Conclusion TUL's superior clinical efficacy may be due in part to anti‐inflammatory benefits mediated by PMN apoptosis and inhibition of CXCL8 in MΦ, which together promote the resolution of inflammation. Supported by Pfizer.