Physiol. Res. 55: 309-316, 2006


Erythropoietin Attenuates Lipopolysaccharide-Induced Splenic and Thymic Apoptosis in Rats

T. F. KOROGLU1, O. YILMAZ2, E. OZER3, H. BASKIN4, N. GOKMEN5,
A. KUMRAL1, M. DUMAN1, H. OZKAN1


1Department of Pediatrics, 2Animal Research Laboratory, 3Department of Pathology, 4Department of Microbiology, 5Department of Anesthesiology, Dokuz Eylul University School of Medicine, Izmir, Turkey

Received April 4, 2005
Accepted July 5, 2005
On-line available August 5, 2005


Summary
Apoptosis of lymphoid tissues during sepsis is well documented and linked to the pathobiology of organ failure and death. In this study, we evaluated the effect of a single dose of recombinant erythropoietin (EPO) on thymic and splenic apoptosis in an endotoxic sepsis model. Young male Wistar rats were divided into 3 groups and administered intraperitoneally (IP) either normal saline; lipopolysaccharide (LPS) 10 mg/kg; or EPO (5000 U/kg) 30 min before lipopolysaccharide. Six hours following LPS administration animals were sacrificed. Apoptosis was assessed by hematoxylin-eosin staining, terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling (TUNEL), and caspase-3 immunostaining. When compared with animals given LPS, animals pretreated with EPO displayed reduced splenic and thymic TUNEL positivity of 443 (p<0.05) and 1434 (p<0.05) nuclei per high power field (hpf), respectively. Caspase-3 positivity was also significantly reduced in the spleen and thymus, with 314 (p<0.05) and 933 (p<0.05) positive stained nuclei per hpf, respectively. Serum nitrite levels were elevated in animals given lipopolysaccharide. Pretreatment with EPO attenuated the increase in nitrite levels; however, this did not reach statistical significance. We conclude that a single dose of recombinant erythropoietin can reduce thymic and splenic apoptosis associated with lipopolysaccharide administration.


Key words
Sepsis Endotoxin Lymphocyte Erythropoietin
 


2006 by the Institute of Physiology, Czech Academy of Sciences