Inflammatory mediator production in swine following endotoxin challenge with or without co-administration of dexamethasone.
The inflammatory response in swine challenged with lipopolysaccharide (LPS) has only been partially characterized. As swine are increasingly used in biomedical research, it is important to determine if they respond to endotoxin challenge in a manner similar to other model systems. Accordingly, 24 Poland China x Landrace barrows were treated with saline, LPS, dexamethasone, or LPS and dexamethasone, with six animals in each treatment group. The kinetics of TNFalpha, IL-1beta, IL-6, IL-8, IL-10, nitric oxide (nitrate/nitrite), and neopterin production in swine plasma were examined at 1, 3, 6, 9, and 24 h after acute LPS challenge. Lipopolysaccharide increased plasma TNFalpha levels, which peaked 1 h post-challenge. Dexamethasone decreased LPS-induced TNFalpha by approximately 60%. Plasma IL-6 levels peaked 3 h post-LPS challenge, returning to basal levels by 9 h. Swine given both LPS and dexamethasone had minimal IL-6 levels. Control and dexamethasone-only treated animals never exhibited systemic TNFalpha or IL-6 levels. Lipopolysaccharide increased plasma IL-10 1 h after challenge. Dexamethasone did not alter plasma IL-10 levels in LPS-challenged swine. Interleukin-1beta was constitutively present in plasma and was not altered by any combination of treatments. Plasma IL-8 was not observed in any treatment group. Plasma nitrate/nitrite levels were maximal 24 h post-challenge. Dexamethasone treatment prevented increases in plasma nitrate/nitrite levels in LPS-treated animals. Lipopolysaccharide induced levels of neopterin; dexamethasone served to further increase plasma neopterin levels in LPS-challenged animals. The discordant regulation of inflammatory mediators suggests that the immunological responses by swine to LPS are distinct from the responses seen in rodent and human studies.
Myers
Michael J
MJ
Division of Animal Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Road, Laurel, MD 20708, USA. mmyers@cvm.fda.gov
Farrell
Dorothy E
DE
Palmer
Douglas C
DC
Post
Lynn O
LO
D000818:Animals; D015415:Biomarkers / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood* / Q000276:immunology; D007275:Injections, Intravenous; D007378:Interleukins / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D019798:Neopterin / Q000097:blood / Q000276:immunology; D009569:Nitric Oxide / Q000097:blood / Q000276:immunology; D013552:Swine / Q000097:blood / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D015415:Biomarkers; D018836:Inflammation Mediators; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019798:Neopterin; D003907:Dexamethasone