Anti-Inflammatory Benefits of Antibiotic-Induced Neutrophil Apoptosis: Tulathromycin Induces Caspase-3-Dependent Neutrophil Programmed Cell Death and Inhibits NF-κB Signaling and CXCL8 Transcription

Tulathromycin Exerts Proresolving Effects in Bovine Neutrophils by Inhibiting Phospholipases and Altering Leukotriene B4, Prostaglandin E2, and Lipoxin A4Production

“…Lipoxins (LXs) are part of a new class of lipid mediators that have gained a significant amount of attention for their potent antiinflammatory and proresolving actions (13). Indeed, LXs, resolvins, and cyclopentenones have been shown to promote macrophage efferocytosis of apoptotic neutrophils, inhibit the production of proinflammatory mediators, and stop inflammatory cell infiltration (13), all effects which we showed were induced by tulathromycin via unclear mechanisms (28,29). Using reverse-phase HPLC methods, we discovered that resting and activated neutrophils secrete LXA 4 upon tulathromycin treatment.…”

“…Tulathromycin has a high affinity for uptake within bovine neutrophils (26). The antimicrobial properties of tulathromycin alone cannot fully explain its effectiveness in clearing the infection and inflammation associated with BRD, and recent observations support the hypothesis that the drug may promote the resolution of inflammation (28,29) via mechanisms that are not fully understood.…”

Direct and Indirect Anti-Inflammatory Effects of Tulathromycin in Bovine Macrophages: Inhibition of CXCL-8 Secretion, Induction of Apoptosis, and Promotion of Efferocytosis

“…A growing body of evidence has also demonstrated that some macrolides such as tilmicosin, tulathromycin, and erythromycin deliver anti-inflammatory benefits by promoting apoptosis in neutrophils (27)(28)(29)(30). However, the effects of macrolides on macrophage survival and cell death in the context of inflammation remain incompletely understood.…”

“…We recently reported that tulathromycin induces caspase-3-dependent apoptosis in bovine neutrophils and inhibits NF-B signaling and LTB 4 synthesis (30). The present study investigated the immunomodulating effects of tulathromycin in bovine macrophages, in hopes to further elucidate the anti-inflammatory mechanisms of this drug in a clinically relevant model system.…”

Efficacy of Tulathromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia

“…Macrolides exert a wide variety of anti‐inflammatory or immunomodulatory effects that might enhance their clinical efficacy including decreased mucus production by epithelial cells and reduced secretion of pro‐inflammatory cytokines by mononuclear and epithelial cells 30. Recent studies indicate that TUL induces apoptosis in bovine neutrophils and macrophages, and inhibits production of pro‐inflammatory mediators by these cells 31, 32, 33. Additional studies will be required to determine the exact mechanism responsible for the efficacy of TUL in the treatment of bronchopneumonia in foals.…”