Cytokines in brain-immune interactions: the influence of brain lateralization P.J. Neveu
INSERM U394, Institut Fran?ois Magendie, rue Camille Saint"Sa¸ns, 33077 Bordeaux, France
The relationships between cytokines and the brain involve two different compartments. In the periphery, cytokines are synthe sized in response to inflammatory, immune or allergic reactions. In the brain, the production of cytokines is involved in neural plas ticity during development and in brain inflammatory and auto immune reactions. Brain cytokines are also involved in physiolog ical, behavioral and neuroendocrine alterations occuring during inflammatory and infectious syndromes. Although these two com partments are separated by the bloodbrain barrier, they can act in a coordinated fashion. The release of cytokines in the periphery induces the production of brain cytokines through different ways including afferent sensory nervous pathways. Conversely, brain cytokines are able to modulate the activity of the immune system including the peripheral production of cytokines. Furthermore, the activity of central and peripheral cytokines depend on brain lat eralization. In experimental animals, the peripheral injection of cytokines induces fever and a sickness behavior characterized by anorexia, depressed activity and loss of interest in their conspe cifics. These behavioral alterations result from a secondary brain production of cytokines. In cancer patients treated with cytokines, the appearance of a depressive symptomatology is correlated with the production of cytokines. As depression depends on lateraliza tion, production of cytokines may also depend on lateralization in these patients. Indeed, in animals the behavioral alterations in duced by cytokines are linked to brain lateralization. Peripheral cytokines also induce modifications of brain metabolism that de pend on lateralization. Furthermore, the stimulation of the corti coid axis by cytokines depends on lateralization. Finally, the pro duction of interleukin1 in response to a psychological stress or the injection of lipopolysaccharide depends on brain lateralization. Experimental and clinical data clearly show that cytokines are molecules involved in the communication between the brain and the immune system. Their effects depend on the individual brain organization as demonstrated by the influence of lateralization. However, the involvement of cytokine receptors in various brain regions remain to be elucidated in order to explain the behavioral and neuroendocrine effects of cytokines. The respective roles of the numerous cytokines that are organized in a complex network, and especially the possible opposite roles of pro and antiinflam matory cytokines need further experimentation.