MONOCYTES AND LYMPHOCYTES AS ACTIVE PARTICIPANTS IN THE PATHOGENESIS OF EXPERIMENTAL SHOCK

We investigated the role played by monocytes and lymphocytes in the pa thogenesis of experimental shock. Splanchnic artery occlusion (SAG) sh ock was induced in anaesthetized rats by clamping splanchnic arteries For 45 min followed by by reperfusion. Sham operated animals were used as controls. SAO shocked rats had a decreased survival time (80 +/- 1 1 min, while sham shocked rats survived more than 4 h), increased seru m (248 +/- 21 U/ml) and macrophage (145 +/- 15 U/ml) levels of TNF-alp ha, enhanced myeloperoxidase activity in the ileum (3.38 +/- 0.2 U x 1 0(-3)/g tissue), decreased number of monocytes, lymphocytes and neutro phils and a profound hypotension. In addition we found an increased ex pression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endot helium and a reduced percentage of VLA-4 positive monocytes and lympho cytes. Inhibition of TNF-alpha synthesis, reversed the increased endot helial expression of VCAM-1, increased the percentage of integrin VLA- 4 positive leukocytes and improved monocyte, lymphocyte and neutrophil count. Furthermore a passive immunization with specific antibodies ra ised against VCAM-1 (2 mg/kg, i.v. 3 h before SAG) increased survival, reduced MPO activity in the Ileum (0.034 +/- 0.04 U x 10(-3)/g tissue ) and improved mean arterial blood pressure, Our data suggest that mon ocytes and lymphocytes participate in the pathogenesis of splanchnic i schaemia-reperfusion injury and may amplify the adhesion of neutrophil s to peripheral tissues.