Impact of combined C1 esterase inhibitor/coagulation factor XIII or N-acetylcysteine/tirilazad mesylate administration on leucocyte adherence and cytokine release in experimental endotoxaemia.
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-1beta (IL-1beta). 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-1beta plasma levels, but increased IL-6 levels.
Birnbaum
J
J
Klinik für Anaesthesiologie und Operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany. juergen.birnbaum@charite.de
Klotz
E
E
Spies
C D
CD
Mueller
J
J
Vargas Hein
O
O
Feller
J
J
Lehmann
C
C
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002448:Cell Adhesion / Q000502:physiology; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy / Q000276:immunology; D005176:Factor XIII / Q000627:therapeutic use*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011281:Pregnatrienes / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D011281:Pregnatrienes; D005176:Factor XIII; D000111:Acetylcysteine; C053355:tirilazad