The Effeet of GM-CSF on the Survival and the Changes in the Liver and Lung in Sptic Mice

Kwun, Koing Bo; Kim, Sang Woon; Song, In Hyung; Yoon, Sung Soo; Choi, Joon Hyuk

Abstract

Sepsis is associated with high mortality, which correlates with the susceptibility of multiple organ dysfunction syndrome in the course of immunoinflammatory response during sepsis. Recently, granulocyte-macrophage colony stimulating factor (GM-CSF) is known to decrease the mortality of animals with severe stress, such as sepsis or thermal injury, by activating immunocytes associated with first line defence mechanism. Although GM-CSF may plays an important role in modulating immunoinflammatory cascade during sepsis, the exact mechanism of action is unclear and the information about the effects on the tissue damage is also poor. To assess the effects of GM-CSF on the mortality rate and on the tissue damage during sepsis, the authors conducted this animal study. Sepsis was induced by injection of 0.5 ml broth containing live Klebsiella pneumoniae (6x109 colony/ml) to the right thigh muscle of the mouse. The sepsis induced group was divided into four groups of 15 rats each. The first group was received normal saline and expressed as sepsis group. The second group was received antibiotics (cefoxitins) and expressed as A group. The third group was received GM-CSF (200 ng/body daily) and expressed as G group. The last group was received antibiotics and GM-CSF and expressed as AG group. The survival rates were obtained from each group. G and AG group showed significant improvement in survival rate compared to the sepsis and A groups (p<0.05). After 72 hours, all animals were sacrificed and submitted for the study of serologic and histologic changes. The level of interleukin-6 was significantly decreased in AG group compared to the sepsis guoup (p<0.05). The level of serum lactate and lung wet/dry ratio were significantly decreased in G group compared to the sepsis group (p<0.05). Glutathione content in liver tissue was significantly increased in the G and AG groups compared to the sepsis and A groups (p<0.05). Microscopic tissue examinations revealed that a significantly higher rate of tissue edema and necrosis, inflammatory cell infilteration, nuclear necrosis and endothelial swelling in sepsis group compare to the treated groups. However there was no significant difference between each treated groups. From these results, the beneficial effects of GM-CSF on the survival rate and tissue damage during sepsis were noted.