AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS: CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P<0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P<0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alpha IL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P<0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P < 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P < 0.01). CONCLUSION: CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.
AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS:CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P<0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P<0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alphaIL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P<0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P < 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P < 0.01). CONCLUSION:CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.
Authors: Judy L Oakes; Brian P O'Connor; Laura A Warg; Rachel Burton; Ashley Hock; Joan Loader; Daniel Laflamme; Jian Jing; Lucy Hui; David A Schwartz; Ivana V Yang Journal: Am J Respir Cell Mol Biol Date: 2012-09-20 Impact factor: 6.914