A growing body of evidence, primarily from animal models of cerebral ischemia 
and preliminary human studies, indicates that inflammatory mechanisms contribute 
to secondary neuronal injury after acute cerebral ischemia. Ischemia followed by 
reperfusion rapidly leads to the expression of inflammatory cytokines, 
particularly tumor necrosis factor-alpha and interleukin-1beta, which stimulate 
a complex cascade of events involving local endothelial cells, neurons, 
astrocytes, and perivascular cells. A secondary response includes the release of 
other cytokines, an increase in components of the coagulation system, an 
upregulation of cell adhesion molecule expression, and changes in the expression 
of components of the immune response. The net effect of these events is 
transformation of the local endothelium to a prothrombotic/proinflammatory state 
and induction of leukocyte migration to the site of injury. A number of studies 
have shown that leukocyte migration occurs within hours of reperfusion. 
Leukocytes accumulate in the injured region, where they cause tissue injury by 
several mechanisms, including occlusion of microvasculature, generation of 
oxygen free radicals, release of cytotoxic enzymes, alteration of vasomotor 
reactivity, and increase in cytokine and chemoattractant release. Monoclonal 
antibodies against leukocyte adhesion molecules have been shown to reduce 
infarct volume in animal models of ischemia-reperfusion. However, this treatment 
failed to show benefit in the Enlimomab Acute Stroke Trial. A number of factors 
may complicate the use of antibody directed adhesion molecule blockade in acute 
stroke and will be discussed in this article. Overall, an increased 
understanding of inflammatory and immunologic mechanisms still offers great 
potential for reducing acute stroke injury.