Impact of Combined C1 Esterase Inhibitor/Coagulation Factor XIII or N-Acetylcysteine/Tirilazad Mesylate Administration on Leucocyte Adherence and Cytokine Release in Experimental Endotoxaemia

Authors: Birnbaum, J.¹; Klotz, E.¹; Spies, C.D.¹; Mueller, J.¹; Vargas Hein, O.¹; Feller, J.¹; Lehmann, C.²

Source: The Journal of International Medical Research, Volume 36, Number 4, July 2008 , pp. 748-759(12)

Publisher: Field House Publishing

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Abstract:

We determined the effects of combinations of C1 esterase inhibitor (C1-INH) with factor XIII and of N-acetylcysteine (NAC) with tirilazad mesylate (TM) during lipo-polysaccharide (LPS)-induced endotoxaemia in rats. Forty Wistar rats were divided into four groups: the control (CON) group received no LPS; the LPS, C1-INH + factor XIII and NAC + TM groups received endotoxin infusions (5 mg/kg per h). After 30 min of endotoxaemia, 100 U/kg C1-INH + 50 U/kg factor XIII was administered to the C1-INH + factor XIII group, and 150 mg/kg NAC + 10 mg/kg TM was administered in the NAC + TM group. Administration of C1-INH + factor XIII and NAC + TM both resulted in reduced leucocyte adherence and reduced levels of interleukin-1β (IL-1β). The LPS-induced increase in IL-6 levels was amplified by both drug combinations. There was no significant effect on mesenteric plasma extravasation. In conclusion, the administration of C1-INH + factor XIII and NAC + TM reduced endothelial leucocyte adherence and IL-1β plasma levels, but increased IL-6 levels.

Keywords: TIRILAZAD MESYLATE; C1 ESTERASE INHIBITOR; COAGULATION FACTOR XIII; N-ACETYLCYSTEINE; INTRAVITAL MICROSCOPY; CYTOKINES; ENDOTOXAEMIA; RATS

Document Type: Research article

Affiliations: 1: Klinik für Anaesthesiologie und operative Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany 2: Department of Anaesthesia, Department of Pharmacology, and Department of Microbiology and Immunology, Victoria General Hospital, Dalhousie University, Halifax, Nova Scotia, Canada