Erythropoietin reduces the development of nonseptic shock induced by zymosan in mice.
OBJECTIVE
Erythropoietin is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. In the present study, we investigated the effects of erythropoietin (1000 IU/kg subcutaneously) on the development of nonseptic shock caused by zymosan.


METHODS
Prospective, randomized study.


METHODS
University-based research laboratory.


METHODS
Male CD mice.


METHODS
Mice received either intraperitoneally zymosan (500 mg/kg, administered intraperitoneally as a suspension in saline) or vehicle (0.25 mL/mouse saline). Erythropoietin was administered at the dose of 1000 IU/kg subcutaneously, 1 and 6 hrs after zymosan administration. Organ failure and systemic inflammation in mice was assessed 18 hrs after administration of zymosan and/or erythropoietin.


RESULTS
Treatment of mice with erythropoietin (1000 IU/kg subcutaneously, 1 and 6 hrs after zymosan administration) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. Erythropoietin also attenuated the lung, liver, and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase activity caused by zymosan in the lung and intestine. Immunohistochemical analysis for nitrotyrosine and poly(ADP-ribose) revealed positive staining in lung and intestine tissues obtained from zymosan-treated mice. The degree of staining for nitrotyrosine and poly(ADP-ribose) was markedly reduced in tissue sections obtained from zymosan-treated mice, which received erythropoietin. In addition, administration of zymosan caused severe illness in the mice characterized by a systemic toxicity, significant loss of body weight, and a 70% mortality rate at the end of observation period (7 days). Treatment with erythropoietin significantly reduced the development of systemic toxicity, the loss in body weight, and the mortality caused by zymosan.


CONCLUSIONS
This study provides evidence, for the first time, that erythropoietin attenuates the degree of zymosan-induced nonseptic shock in mice.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Messina, Italy.
Di Paola
Rosanna
R
Mazzon
Emanuela
E
Patel
Nimesh S A
NS
Genovese
Tiziana
T
Muià
Carmelo
C
Crisafulli
Concetta
C
Caputi
Achille P
AP
Thiemermann
Christoph
C
D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D012769:Shock / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D015054:Zymosan / Q000008:administration & dosage
D004921:Erythropoietin; D015054:Zymosan