Leukocyte, plasma, and organ-associated cytokine profiles in an animal model of acute inflammation.
Systemic administered lipopolysaccharide (LPS) induces a cytokine response in peripheral blood without correlations with cytokine content at the organ level. We hypothesised (1) that cytokine mRNA expression in peripheral blood mononuclear cells (PBMCs) preceded the plasma cytokine increase during endotoxaemia and (2) that statins as anti-inflammatory agents modified the LPS-induced cytokine responses. 30 pigs were randomised into 3 groups: placebo (I) or atorvastatin 80 mg (II) for 21 days, followed by LPS-infusion on day 22, or controls (III). LPS was infused at increasing concentrations (2.5 to 15 microg/kg/h) for 30 min, followed by sustained infusion (2.5 microg/kg/h) for 330 min. We measured plasma IL-6, IL-10, and TNF-alpha, and their mRNA expression in PBMCs during the LPS-infusion, and the cytokine content in kidney and heart biopsies at 360 min. LPS reduced TNF-alpha mRNA in PBMCs at 60 min, whereas IL-6 mRNA increased at 240 min. There were no correlations with plasma cytokines, which peaked at 60 min (IL-10 and TNF-alpha) and 240 min (IL-6). Cytokine content did not increase in organs, and no effects of statins could be demonstrated. In conclusion, LPS-infusion reduced leukocyte TNF-alpha mRNA and increased IL-6 mRNA, whereas plasma TNF-alpha, IL-6, and IL-10 increased markedly.
Ebdrup
Lotte
L
Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark. lotteebdrup@dadlnet.dk
Krog
Jan
J
Granfeldt
Asger
A
Larsen
Pernille Ø
PØ
Vestergaard
Christian
C
Hokland
Marianne
M
Tønnesen
Else
E
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000069059:Atorvastatin; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D019446:Endotoxemia / Q000097:blood / Q000276:immunology / Q000473:pathology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D011758:Pyrroles / Q000008:administration & dosage; D011897:Random Allocation; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011758:Pyrroles; D000069059:Atorvastatin