title: Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.
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)-α, interleukin (IL)-6 and IL-1β 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 1.25μg/mL LPS, the levels of TNF-α, IL-1β 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-α 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.
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: Heidi.Wyns@UGent.be.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wyns
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Plessers
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Watteyn
authors.affiliation: Department of Surgery and Anaesthesia of Domestic Animals, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: van Bergen
authors.affiliation: Department of Surgery and Anaesthesia of Domestic Animals, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Stijn
authors.initials: S
authors.lastname: Schauvliege
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Siegrid
authors.initials: S
authors.lastname: De Baere
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Mathias
authors.initials: M
authors.lastname: Devreese
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Backer
authors.affiliation: Department of Pharmacology, Toxicology & Biochemistry, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Siska
authors.initials: S
authors.lastname: Croubels
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy; D007660:Ketoprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D018942:Macrolides / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D013552:Swine; D013553:Swine Diseases / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D018942:Macrolides; D007660:Ketoprofen; D015232:Dinoprostone; C552399:gamithromycin
keywords: Gamithromycin; Interleukin-1β; Interleukin-6; Ketoprofen; Lipopolysaccharide; PBMC; Pig; Prostaglandin; Tumour necrosis factor-α