The effects of recombinant human granulocyte‐colony stimulating factor on vascular dysfunction and splanchnic ischaemia‐reperfusion injury

Abstract

1 The aim of our study was to investigate the eects of recombinant human granulocyte-colony stimulating factor in a rat model of splanchnic ischaemia-reperfusion injury. 2 Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock; SAO shock). Sham operated animals were used as controls. Survival rate, serum tumour necrosis factor-a (TNF-a), neutrophil count, bone marrow myeloid precursor cells, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation), mean arterial blood pressure and the responsiveness of aortic rings to phenylephrine (PE, 1 nM ± 10 mM) were studied. 3 SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), increased serum levels of TNF-a (201+10 u ml 71

Neuroprotective Effect of Granulocyte Colony–Stimulating Factor After Focal Cerebral Ischemia

“…Indeed, reduced neutrophil infiltration in lung and ileum has been observed in a model of splanchnic ischemia and reperfusion 15 minutes after the administration of G-CSF and reperfusion of the small bowel. 29 In accordance with these findings, we did not observe in the present study an increase of neutrophil infiltration into the ischemic hemisphere, although total neutrophilic blood count increased after G-CSF treatment. Reduced cytokine toxicity may also limit interactions between neutrophils and the endothelium in microvessels and improve microvascular flow in the penumbra.…”

Neuroprotective Effect of Recombinant Human Granulocyte Colony-Stimulating Factor in Transient Focal Ischemia of Mice

“…This conclusion is consistent with recent evidence that inhibition of iNOS gene provides protection against cerebral ischemia. Previous studies showed that G-CSF protects against death in a nonseptic model of ischemia/reperfusion injury and concluded that such beneficial effect is the consequence of either reduction of TNF-a or inhibition of iNOS activity (Gorgen et al, 1992;Kitabayashi et al, 1995;Squadrito et al, 1997). Moreover, other investigators showed that G-CSF decreased the level of IL-1b, IL-6, and IL-8 under several conditions (Hebert et al, 1997;Heard et al, 1998;Heard and Fink, 1999).…”

“…One of the main mechanisms of action for this effect is activation of the JAK/STAT pathway through intracellular signaling from G-CSF-G-CSF receptor binding in cerebral ischemia, which could be induced after activation of the antiapoptotic cascade (Konishi et al, 1993;Fukada et al, 1996;Shimozaki et al, 1997). Another nonhematopoietic effect of G-CSF is antiinflammatory action mediated by inhibition of the inducible nitric oxide synthase (iNOS) activity, as shown in splanchic ischemia/reperfusion injury (Squadrito et al, 1997). Other studies reported the relationships between G-CSF and glial activation (Zavala et al, 2002).…”

The Effects of G-CSF Treatment and Starvation on Bacterial Translocation in Hemorrhagic Shock

“…Finally, it is possible that G-CSF treatment improves the impaired splanchnic perfusion and this may also help attenuate the rate of bacterial translocation in hemorrhagic shock. The salutary effects of G-CSF on the impaired hemodynamic parameters of experimental animals subjected to bacterial challenge were previously shown [27], and it is reported that recombinant human G-CSF improved the vascular dysfunction in splanchnic ischemia-reperfusion injury by a mechanism(s) that does not depend upon its hematopoietic effects in a nonseptic model of shock [28].…”