The Effect of Cortisone on Generalized Shwartzman Reaction

Kim, Hyo Youl; Han, Byoung Geun; Choi, Seung Ok; Lee, Kwang Hoon

Abstract

A generalized Shwartzman reaction(gSr) is characterized by vascular injury with microvascular fibrin deposition, leukocyte aggregation and hemorrhagic lesions in various organs and elicited by endotoxin from gram-negative bacteria. Leukocyte adherence to endothelial cells has been regarded as a pivotal event in this type of neutrophil mediated inflammatory response. Recently, it was described that leukocyte adhesion to endothelium is facilitated by the adhesion molecules, such as LFA-1(CDIIa/CD18) or Mac-1 (CDllb/CD18) binding to intercellular adhesion molecule-1(ICAM-1). To investigate the role of cell adhesion molecules in inflammatory vascular injury, the authors examined the expression of cell adhesion molecules, ICAM-1 and CD18, in gSr. Group A(n=5) received two injections of lipopolysaccharide(LPS) from E. coli 055:B5; 200 microgram/kg and 200 microgram/kg 24hours apart. Group B(n=5) received one dose of LPS(200 microgram/kg) after glucocorticoid treatment(methylprednisolone, 25mg/kg/day). Group C(n=5) received single dose of LPS(200 microgram/kg). The control group(n=3) received two injections saline instead of LPS. Animals were sacrificed four hours after the last dose of LPS or saline, The results were as follows: 1) Group A and B showed numerous fibrin micro-thrombi, inflammatory cell infiltration and some he-morrhagic change in kidney and lung, but group C and the control group did not show any lesions. In kidney the degree of fibrin deposition by IF was significantly increased in group A and B when compared to group C(p<0.05). 2) ICAM-1 was expressed by vascular endothelium including glomerular capillaries and some lymphocytes in the control group, This expression was increased in group C. But, group A and B was significantly decreased in ICAM-1 expression, especially in kidney comparing with group C and the control group(p<0.05). 3) Group A and B were significantly increased in CD18 expressing cells in glomerulus when compared with the control group(p<0.05). The number of CD18 expressing cells in glomerulus correlated significantly with a degree of fibrin deposition. In conclusion, these results suggest that the development of gSr requires the adhesion of activated inflammatory cells especially neutrophils to vascular endothelium and these are achieved by the interaction of adhesion molecules like ICAM-1 and CD18. Replacing the LPS with a glucocorticoid also expressing ICAM-1 on endothelium and prepares for leukocyte adhesion to endothelium.