Leukocyte, plasma, and organ-associated cytokine profiles in an animal model of acute inflammation
Ebdrup L, Krog J, Granfeldt A, Larsen PØ, Vestergaard C, Hokland M, Tønnesen E. Leukocyte, plasma, and organ-associated cytokine profiles in an animal model of acute inflammation. APMIS 2008;116:352–60.
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 μg/kg/h) for 30 min, followed by sustained infusion (2.5 μg/kg/h) for 330 min. We measured plasma IL-6, IL-10, and TNF-α, 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-α 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-α) 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-α mRNA and increased IL-6 mRNA, whereas plasma TNF-α, IL-6, and IL-10 increased markedly.