Cytokines and reperfusion injury

There is increasing evidence that the inflammatory response plays an important role in the potentiation of central nervous system (CNS) ischemic injury. Much of this inflammatory response appears to be mediated by interleukins (IL), a multifunctional subclass of cytokines. The proinflammatory interleukins, including IL-1, tumor necrosis factor alpha(TNF-α), and IL-6, can influence the function and synthesis of other cytokines by a complex cytokine network.1 These proinflammatory interleukins are produced by a variety of cells, including microglial cells, astrocytes, and leukocytes, and appear to directly modulate CNS cell apoptosis, differentiation, and proliferation and to influence subsequent infiltration by leukocytes.1,2 Increased levels of IL-1, TNF-α, and IL-6 have been observed after experimental CNS ischemia.2,3 Indirect evidence for the involvement of interleukins in ischemic injury comes from several recent clinical studies which found that CSF and plasma levels of IL-6 predict the functional recovery of the patient and also correlate with the infarct size.4,5 The strongest support for the important role played by the inflammatory response in CNS ischemia comes from studies investigating the role of leukocyte adhesion and infiltration after stroke. A large number of studies have now shown that leukocytes adhere and infiltrate early after CNS ischemia and that agents that block leukocyte adhesion produce therapeutic benefits in a variety of animal models.6-8 Recent evidence suggests that cytokines may be key components in the activation and recruitment of leukocytes into the CNS. IL-1β, TNF-α, and IL-6 activate leukocytes and increase the expression of adhesion receptors on the leukocyte (CD-18) and on endothelial and astrocyte cells (intercellular adhesion molecule [ICAM]-1).2,9 The preceding evidence suggests that the inflammatory response is an important component of CNS ischemic injury and that the interleukins appear to play a key role in the modulation of this inflammatory response. By modulating the …