Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.

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Wyns H, Meyer E, Plessers E, Watteyn A, van Bergen T, Schauvliege S, De Baere S, Devreese M, De Backer P, Croubels S

Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.

Vet Immunol Immunopathol. 2015 Dec 15;168(3-4):211-22. doi: 10.1016/j.vetimm.2015.09.014. Epub 2015 Sep 28.

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26547885 [ View in PubMed
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Abstract

The immunomodulatory properties of gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25mug/mL LPS, the levels of TNF-alpha, IL-1beta and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-alpha and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.

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