Cytokines and the central nervous system

Cytokines are involved both in the immune response and in controlling vario us events in the central nervous system, that is, they are equally immunore gulators and modulators of neural functions and neuronal survival. On the o ther hand, cytokine production is under the tonic control of the peripheral and the central nervous system and the cytokine balance can be modulated b y the action of neurotransmitters released from nonsynaptic varicosities [1 31]. The neuroimmune interactions are therefore bidirectional- cytokines an d other products of the immune cells can modulate the action, differentiati on, and survival of neuronal cells, while the neurotransmitter and neuropep tide release play a pivotal role in influencing the immune response, Cytoki nes and their receptors are constitutively expressed by and act on neurons in the central nervous system, in both its normal and its pathological stat e, but cytokine overexpression in the brain is an important factor in the p athogenesis of neurotoxic and neurodegenerative disorders. Accordingly, it can be accepted that the peripheral and central cytokine compartments appea r to be integrated, and their effects might synergize or inhibit each other ; however. it should always be taken into account that they are spatiotempo rally differentially regulated. New concepts are reviewed in the regulation of relations between cytokine balance and neurodegeneration, including int racellular receptor-receptor, cell-cell, and systemic neuroimmune interacti ons that promote the further elucidation of the complexities and cascade of the possible interactions between cytokines and the central nervous system . (C) 2001 Elsevier Science Inc.