REGULATION OF CYTOKINE AND CHEMOKINE PRODUCTION BY TRANSMITTERS AND COTRANSMITTERS OF THE AUTONOMIC NERVOUS-SYSTEM

The sympathetic nervous system innervates immune organs and, when acti vated, releases its signaling molecules in the vicinity of immune cell s. The released molecules include the ''classical'' transmitters norep inephrine and epinephrine and the co-transmitters ATP and adenosine. I mmune cells express various adrenergic and purinergic receptors that a re sensitive to these molecules, and the production of immune/inflamma tory mediators (cytokines, chemokines, and free radicals) is modulated by activation of these receptors. Notably, the production bf tumor ne crosis iactor-alpha, interleukin-6, -10, and -12, and the chemokine ma crophage inflammatory protein 1 alpha and the production of the free r adical nitric oxide, produced by the inducible nitric oxide synthase, have been shown to be altered by activation of these receptors. Altera tions in the production of the immune mediators may contribute to the development of various diseases. On the other hand, novel experimental therapies based on the modulation of adrenergic or purinergic recepto rs on immune cells are emerging. Such approaches may have beneficial e ffects in limiting tissue injury and suppressing symptoms in certain p athophysiological states. (C) 1998 Elsevier Science Inc.