Details

Autor(en) / Beteiligte

• Hofer, Stefan
• Eisenbach, Christoph
• Lukic, Ivan K
• Schneider, Lutz
• Bode, Konrad
• Brueckmann, Martina
• Mautner, Sven
• Wente, Moritz N
• Encke, Jens
• Werner, Jens
• Dalpke, Alexander H
• Stremmel, Wolfgang
• Nawroth, Peter P
• Martin, Eike
• Krammer, Peter H
• Bierhaus, Angelika
• Weigand, Markus A

Titel

Pharmacologic cholinesterase inhibition improves survival in experimental sepsis

Ist Teil von

• Critical care medicine, 2008-02, Vol.36 (2), p.404-408

Ort / Verlag

Hagerstown, MD: by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• OBJECTIVE:Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic anti-inflammatory pathway. Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo. DESIGN:Prospective, randomized laboratory investigation that used an established murine sepsis model. SETTING:Research laboratory in a university hospital. SUBJECTS:Female C57BL/6 mice. INTERVENTIONS:Sepsis in mice was induced by cecal ligation and puncture. Animals were treated immediately with intraperitoneal injections of nicotine (400 μg/kg), physostigmine (80 μg/kg), neostigmine (80 μg/kg), or solvent three times daily for 3 days. MEASUREMENTS AND MAIN RESULTS:Treatment with physostigmine significantly reduced lethality (p ≤ .01) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p ≤ .05). Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-κB (p ≤ .05) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 (p ≤ .001), and pulmonary neutrophil invasion (p ≤ .05). Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. CONCLUSIONS:Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use.