title: Continuous therapeutic epinephrine but not norepinephrine prolongs splanchnic IL-6 production in porcine endotoxic shock.
abstract: Catecholamines play a central role in the treatment of sepsis-associated hypotension. However, these hormones have also been shown to modulate the lipopolysaccharide (LPS)-induced induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-10, and IL-6 in vitro and in human endotoxemia. We hypothesized that catecholamines applied therapeutically in septic shock also influence cytokine patterns. We studied the cytokine response in tissues of the splanchnic compartment in a porcine endotoxin shock model up to 4 h. Shock was induced by a short infusion of LPS, and animals were treated either with fluid resuscitation alone or in combination with continuous epinephrine or norepinephrine. Animals, receiving epinephrine therapy, showed a significantly prolonged upregulation of IL-6 mRNA expression at 4 h after LPS application in liver (P = 0.0014), spleen (P < 0.0001), and mesenteric lymph nodes (P = 0.0078) as compared with animals treated with norepinephrine or fluid resuscitation. Serum IL-6 increased over time in all groups. The total concentration of the cytokine (area under the curve) was significantly higher in the epinephrine group as compared with the norepinephrine and fluid resuscitation groups (P = 0.017). The peak of serum tumor necrosis factor alpha at 1 h after LPS application was already significantly reduced by epinephrine, which was only administered at a mean of less than 0.05 microg/kg/min at this time point (P < 0.01). None of the catecholamines had a significant effect on IL-10 serum levels when compared with animals receiving fluid resuscitation alone. Our data suggest that the therapeutic application of epinephrine but not of norepinephrine is associated with a profound effect on the IL-6 response of splanchnic reticuloendothelial tissues.
authors: Department of Surgery, University of Vienna, Austria.
authors: Michael
authors: M
authors: Bergmann
authors: Alexander
authors: A
authors: Gornikiewicz
authors: Dietmar
authors: D
authors: Tamandl
authors: Ruth
authors: R
authors: Exner
authors: Erich
authors: E
authors: Roth
authors: Reinhold
authors: R
authors: Függer
authors: Peter
authors: P
authors: Götzinger
authors: Thomas
authors: T
authors: Sautner
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D009638:Norepinephrine / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012769:Shock / Q000628:therapy*; D013152:Splanchnic Circulation; D013154:Spleen / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D016753:Interleukin-10; D012313:RNA; D009638:Norepinephrine; D004837:Epinephrine