erythropoietin ( epo ) is a 34 kda glycoprotein hormone that controls the proliferation , differentiation , and survival of erythroid progenitor cells through an antiapoptotic mechanism .
it has become apparent that epo protects many organs , including brain , heart , kidney and liver , against the injury caused by ischaemia / reperfusion , hemorrhagic shock and systemic inflammation . in this issue of critical care , kao and colleagues  
they found that recombinant human epo ( 400 iu / kg ) exerts significant beneficial effects when it is given as late as 18 hours after caecal ligation and puncture ( clp ) .
although epo had no effect on the ( small ) decline in blood pressure , the decline in platelet and white blood cell counts , or the rise in lactate , it significantly increased tissue perfusion and reduced tissue hypoxia . within 18 hours after clp there was a decline in the number of perfused capillary beds ( reduced oxygen delivery ) ; this , in turn , resulted in an impairment in mitochondrial electron transport and hence respiration ( measured as increase in mitochondrial nadh fluorescence ) in skeletal musle ( extensor digitorum longus ) .
most notably , epo rapidly ( within 10 min ) reversed both of these effects of clp , and hence it increased the number of patent capillaries and increased mitochondrial function .
unfortunately , the authors did not measure any parameters of organ injury and dysfunction , and the model of clp used did not ( within 24 hours ) result in any deaths .
thus , it remains to be seen whether the improvement in oxygen delivery or mitochondrial function afforded by epo also results in a significant improvement in outcome .
the study by kao and coworkers   is of particular importance because epo protects the brain , heart , kidney   and liver   against the tissue injury and dysfunction caused by ischaemia / reperfusion ( for review ) .
the pathophysiology of the shock associated with trauma / haemorrhage also comprises elements of ischaemia / reperfusion injury ( because of hypovolaemia and resuscitation ) as well as excessive inflammation . in 2004
, we reported that administration of epo ( 300 iu / kg intravenously ) upon resuscitation reduced the renal dysfunction and liver injury caused by severe haemorrhage and resuscitation in rat .
these beneficial effects of epo were associated with a reduction in tissue ( renal ) apoptosis secondary to prevention of activation of caspase-3 , -8 and -9 .
interestingly , epo also prevents motor neurone apoptosis and associated neurological disability in an experimental model of spinal cord injury .
low doses of epo ( 300 iu / kg intravenously ) did not affect the organ injury / dysfunction caused by high doses ( 6 mg / kg ) of the toll - like receptor-4 agonist lipopolysaccharide ( lps ) within 6 hours in the rat . however , higher doses of epo ( 4,000 iu / kg given 30 min before lps ) attenuated the renal dysfunction ( decline in glomerular filtration rate ) , which occurred at 16 hours after injection of low - dose lps ( 2.5 mg / kg intraperitoneally ) in mouse .
this beneficial effect of epo in murine endotoxaemia was not due to effects of epo on either renal blood flow or apoptosis , but it was associated with prevention by epo of a fall in renal tissue superoxide dismutase activity associated with endotoxaemia .
thus , mitra and coworkers   concluded that the observed beneficial effects of epo in murine endotoxaemia are secondary to both antioxidant and anti - inflammatory effects of epo , which have been reported in other models of disease .
thus , the beneficial effects of epo in rodent models of endotoxaemia may vary with doses of epo and lps , as well as species ( rat or mouse ) used .
interestingly , higher doses of epo reduce both the systemic inflammation and the organ injury caused by the toll - like receptor-2 agonist zymosan in mouse . specifically , treatment of mice with epo ( 1,000 iu / kg subcutaneously , 1 and 6 hours after zymosan ) attenuated the signs of local ( peritoneal exudation ) and systemic ( lung inflammation ) , as well as organ ( lung , liver and pancreas ) injury and dysfunction ( kidney ) caused by zymosan .
most notably , epo reduced the high mortality ( 70% ) caused by zymosan over the observation period of 7 days .
the reported beneficial effects of epo in preclinical models of shock , trauma and haemorrhage are exciting , but further studies are warranted to determine the effects of epo on outcome ( organ injury / dysfunction and survival ) in models of clp .
interestingly , in 86 patients admitted to a long - term acute care facility , administration of weekly recombinant human epo ( n = 42 ) resulted in a significant reduction in exposure to allogeneic red blood cell transfusion and higher haemoglobin levels than placebo ( n = 44 ) during the initial 42 days of epo therapy .
although not significant , the mortality rates in patients treated with epo ( 12% ) were lower than in the patients treated with placebo ( 23% ) .
the author is funded by the william harvey research foundation ( unrestricted research grant ) to study the tissue - protective effects of epo and has presented a number of invited lectures in this area of research .
 erythropoietin protects many organs against the tissue injury and dysfunction caused by ischaemia / reperfusion and excessive inflammation . 
 this editorial comment discusses the effects of erythropoietin in preclinical models of septic shock , endotoxemia , hemorrhagic shock , spinal cord trauma and zymosan - induced multiple organ failure . 
None
Competing interests