INDUCTION OF CYTOKINES, CHEMOKINES AND ADHESION MOLECULE MESSENGER-RNA IN A RAT FOREBRAIN REPERFUSION MODEL

Cellular damage secondary to reperfusion following ischemic insult has been hypothetically attributed to an inflammatory cascade concerted b y cell-to-cell interactions. While the role of several cytokines and a dhesion molecules in reperfusion injury of the brain has been explored to a certain extent, their regulatory and temporary profiles remain u nclear. We have addressed the temporal features of the induction of mR NA for proinflammatory cytokines, adhesion molecules and chemokines at an acute phase subsequent to reperfusion in rat forebrain. Semiquanti tatively calibrated reverse transcription-polymerase chain reaction an alysis was employed to assess the relative expression of mRNA for inte rcellular adhesion molecule (ICAM)-1, interleukin (IL)-1 alpha, IL-1 b eta, IL-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-g amma, monocyte-chemoattractant protein (MCP)-1, and macrophage migrati on inhibitory factor (MIF). The increase in mRNA from the basal levels after reperfusion followed one of two different patterns; an increase occurring as early as 1 h, or a slight increase continuing up to 24 h after reperfusion. The former pattern was seen for ICAM-1, IL-1 alpha , IL-1 beta, TNF-alpha, and MCP-1, and the latter for IL-6 and MIF. Th ese results were consistent with the proinflammatory properties of the immediately induced cytokines, which may be involved in the initiatio n step of the inflammatory cascade, causing the secondary cellular res ponses and finally leading to further brain damage.