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Anti‐inflammatory benefits of an antibiotic via modulation of neutrophil and macrophage function: The example of tulathromycin
Author(s) -
Fischer Carrie Dawn,
Beatty Jennifer K,
Morck Douglas W,
Lucas Merlin J,
Robb Edward J,
Buret Andre G
Publication year - 2009
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.23.1_supplement.572.12
Subject(s) - lipopolysaccharide , apoptosis , phagocytosis , nitric oxide , inflammation , zymosan , immune system , microbiology and biotechnology , macrophage , antibiotics , immunology , chemistry , biology , biochemistry , in vitro , endocrinology
The pathogenesis of bacterial‐induced inflammatory diseases is due, in part, to the host immune response. The ability of an antibiotic to modulate immune cell function during infection may confer anti‐inflammatory benefits. Tulathromycin (TUL), an antibacterial agent for bovine respiratory disease, is a novel model for investigating immuno‐modulating effects of antibiotics. Studies have shown that TUL exerts pro‐apoptotic effects in bovine neutrophils (PMN). Nuclear factor‐¿B (NF¿B), a transcription factor implicated in the onset of inflammation, is known to inhibit apoptosis. The effects of TUL on macrophage function are unclear. Aims To investigate the mechanisms of TUL‐induced PMN apoptosis and to determine the effects of TUL on bovine macrophage (MØ) function. Results ELISA revealed TUL‐induced PMN apoptosis is caspase‐3 and ‐8 dependent. Western blotting showed TUL reduces phosphorylation of NF¿B inhibitor, I¿B, in zymosan‐stimulated PMN. Light microscopy suggested TUL stimulates phagocytosis of apoptotic PMN in MØ. ELISA and Greiss reaction showed TUL reduced secreted levels of pro‐inflammatory interleukin‐8 and nitric oxide in E. coli lipopolysaccharide‐challenged MØ. Conclusion Modulation of PMN and MØ function by TUL is associated with inhibition of NF¿B signaling . These findings illustrate novel mechanisms through which an antibiotic may deliver anti‐inflammatory benefits.