Cytokines in neuronal cell types.

Cytokines are signals in the immune system, and may have effects on cells distant from the cells of origin. These proteins have been suggested as messengers in the communication between the immune system and the nervous system, in which signals travel only short distances. Neuroimmune interactions have been discussed in view of findings that nervous signals are important for the immune response. The occurrence of neurotransmitter receptors on lymphocytes and cytokine receptors on nerve cells or glia has initiated further studies e.g. on the localization of different cytokines in the nervous system and on long and short term actions of cytokines in the nervous system. Interleukin-1 has been studied extensively along these lines, and found to occur in the nervous and endocrine system, for example in the adrenal chromaffin cells, and to have effects such as induction of slow-wave sleep and stimulation of adrenocortical and gonadotropic hormones. Other cytokines implicated as signals in neuroimmune interactions are IL-2, IL-6, IFN-gamma and TNF-alpha. The functional studies suggest the occurrence of cytokine receptors in the brain, and experiments using 125iodine-labelled IL-1 alpha demonstrate differential distribution of binding sites in the mouse brain. Recently, evidence emerged of an endogenous receptor antagonist for IL-1, which may prove useful for the understanding of the mechanisms of IL-1's actions in the nervous system. A role for cytokines in regulation of the immune response but also in adjusting the organism to the host reaction is implicated. Furthermore, several findings indicate their role as growth promoting factors, and for example the induction of NGF production by IL-1 suggests involvement of this cytokine in regeneration and development in the nervous system. The significance of neuronally produced cytokines may be based upon the anatomically distinct releasing sites that the specific synaptic organization of the nervous system offer and future studies should determine whether cytokines act as neurotransmitters.