[The expression of ICAM-1 and cytokines in the reperfusional state]

With a hypothesis that an inflammatory cascade composed of cell-to-cell interactions causes cellular damage secondary to reperfusion, I studied the temporary profiles of expression of intracellular adhesion molecule (ICAM)-1 and associating induction of proinflammatory cytokines in an acute phase following reperfusion of rat forebrain. Immunohistologically, ICAM-1 expression began to increase 1 hr after reperfusion in the microvessels of the subcortical region and the basal ganglia. Also, leukocyte positive of lymphocyte function associated antigen (LFA)-1 appeared attached to the capillary vessel walls 6 hrs after reperfusion. Semiquantitatively calibrated RT-PCR analysis was employed to assess the relative expression of mRNA. Increase of the mRNAs from the basal levels after reperfusion followed two different patterns; one, seen for ICAM-1, interleukin (IL)-1 alpha, beta, tumor necrosis factor (TNF)-alpha, and monocyte-chemoattractant protein (MCP)-1, exhibited an increase as early as 1 hr, and another, for IL-6 and macrophage migration inhibitory factor (MIF), showed a gradual increase up to 24 hr after reperfusion. The results were consistent with the proinflammatory properties of those immediately-induced cytokines, which may be involved in the initiation step of the inflammatory cascade, causing the secondary cellular responses. Furthermore, I found that MIF protein was expressed in neuropils in the cortex and basal ganglia by immunohistochemistry. Although precise pathophysiological role of MIF is still unclear, this protein may modulate immune reaction by leukocytes in secondary tissue damage following reperfusion stress. Clinically, I investigated soluble ICAM-1 in sera of patients with various cerebral ischemic diseases of acute stage (n = 28) and healthy adults (n = 23). The serum levels of sICAM-1 in patients with ischemic diseases, particularly with transient ischemic attack (TIA), were significantly higher (p < 0.01) than those of healthy individuals. These results together indicate that cell-cell interaction by adhesion molecules and cytokines is an important component in the pathogenesis of ischemic cerebral diseases, especially at the acute phase.