Matrix metalloproteinase and cytokine profiles in monocytes over the course of stroke

Stroke is a common cause of death and disability in our society. Stroke is associated with changes in immune responses within the central nervous syst em as well as systemically. The cel Is contributing to such changes as well as the factors contributing to formation of the inflammatory infiltrate ob served in stroke remain to be clarified. In this study, blood monocytes and corresponding mononuclear cells (MNC) were separated and examined in paral lel within 4 days and 1-3 months after onset of ischemic stroke. Numbers of TNF-alpha-, IL-12-, IL-6-, and IL-10-secreting cells and of cells expressi ng mRNA for matrix metalloproteinase (MMP)-1, -2, -7, -9 and tissue inhibit or of MMP (TIMP)-1 were studied. The TNF-alpha-, IL-12-, and IL-6-secreting monocytes and MNC were elevated during the acute phase compared to healthy controls. Such differences were not observed when stroke patients were exa mined during convalescence. The IL-10-secreting monocytes did not change ov er the course of stroke. Levels of monocytes expressing MMP-1, MMP-7 and TI MP-1 mRNA were elevated in the acute phase of stroke patients compared to c onvalescence and healthy controls, as were levels of MMP-1, -2, -7, -9 and TIMP-1 mRNA expressing blood MNC. The MMP-2 and -9 activity as measured by zymography also was higher in MNC supernatants in the acute phase of stroke compared to convalescence. The high levels of proinflammatory cytokines an d MMPs in blood monocytes and MNC further demonstrate the presence of syste mic aberrations in the acute phase of stroke. Such changes may contribute t o the influx of blood-borne cells into the ischemic lesions during the acut e phase of stroke.