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Abstract

Objectives

To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-α) in lungs of calves experimentally infected with Pasteurella haemolytica.

Animals

12 weight-ranked Holstein calves.

Procedure

Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 × 108 P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3- hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. Soluble TNF-α and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA.

Results

Treatment with tilmicosin resulted in significant (P< 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-α concentrations were not significantly affected by tilmicosin.

Conclusion

Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function.

Clinical Relevance

By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs. (Am J Vet Res 1998;59:765-771)

Free access
in American Journal of Veterinary Research

SUMMARY

The antibiotic polymyxin B sulfate is a cationic polypeptide with a unique cyclical configuration and distinct cationic characteristics. In this investigation, polymyxin H was evaluated to determine its ability to prevent synthesis of lactic acid and tumor necrosis factor-α (tnf-α) by lipopolysaccharide-stimulated strain RAW 264.7 macrophage-like cell populations. In this context, gradient concentrations of polymyxin B were formulated in the presence of fixed concentrations of lipopolysaccharide fractions from Escherichia coli (B4:0111), E coli (J5), Klebsiella pneumoniae, Pseudomonas aeruginosa. Salmonella minnesota, and S typhimurium (Re). Quantitation of tnf-α was established by the application of a tissue culture-based biological assay system, using the WEHI 164 clone 13 indicator cell line. Investigations also included evaluation of the ability of gradient concentrations of lipopolysaccharide fractions from E coli (B4:0111), E coli Q5), K pneumoniae, P aeruginosa, S minnesota, and S typbimurium (Re) to form a complex with polymyxin B. This was established through application of high-performance thin-layer chromatography techniques. On the basis of the known molecular characteristics of lipopolysaccharide, its lipid A-core subfractions, and polymyxin B, these results imply that cytoprotective properties of polymyxin B are attributable to direct interaction and subsequent complex formation. More specifically, the mechanism by which polymyxin B exerts affinity for lipopolysaccharide fractions is proposed to occur through attractive ionic interactions established between the cationic diami-nobutyric acid residues of polymyxin B and the mono- or diphosphate group(s) of the lipid A-corc moiety. It is highly probable that this molecular phenomenon is accompanied by hydrophobic interactions established between the terminal methyloctanoyl or methylheptanoyl groups of polymyxin B and the saturated carbon chains of the lipid A-core subfraction of lipopolysaccharide fractions

Free access
in American Journal of Veterinary Research

potent cytokines released by myeloid cells, such as TNFα and IL-1, promotes a cascade of events that results in sequestration of polymorphonuclear leukocytes in tissues and parenchymal dysfunction. 11 Inflammatory responses are beneficial in recognition

Full access
in American Journal of Veterinary Research

; leukocyte count; and plasma concentrations of TNF-α, interleukin-6, thromboxane B 2 , and prostaglandin F 1 α . 26 Transient tachypnea, sweating, and increased plasma thromboxane concentration associated with polymyxin B-dextran 70 conjugate usage (with or

Full access
in American Journal of Veterinary Research

elicited during inflammation are extensive, some of the cytokines associated with altered CYP values include IL-1β, IL-6, TNF-α, IFN-α, IFN-β, and IFN-γ. 1 Cytokine production during infection and inflammation reduces both constitutive and induced CYP

Full access
in American Journal of Veterinary Research