Behavior-immunity relationship: The role of cytokines

There are several phenomena in which the immune and the central nervous sys tems regulate each other. However, their mechanisms are poorly understood. Since cytokines have a central role in the regulation of the immune respons e, this review describes their participation in two forms of neuro-immune c ommunication, immunomodulation by psychological stress and behavioral condi tioning of immune response. The role of cytokines in the endocrine and beha vioral effects of acute phase, where cytokines have an effect in functions of the central nervous system, is also reviewed. The effects of psychologic al stress are described as both inmunosuppressing and immunoenhancing. Amon g them, a relevant immunosuppressing one is the reduction of IL-1, IL-2, an d IFN-gamma levels. In contrast, some of the pro-inflammatory effects of st ress are mediated by an increase in the levels of LL-6, IL-1, and TNF media ted by the neurotransmitter Substance P. A possible role for IL-1 and IFN-b eta as possible messengers in immune regulation by behavioral conditioning is proposed. Pro-inflamatory cytokines in turn can activate the hypothalamu s-pituitary-adrenal axis and induce sickness behavior during the acute phas e response, during which the parasympathetic nervous system. serves as path way for their detection by the central nervous system. An account is given about recent findings on the regulation of cytokine expression by neurotran smitters from the sympathetic nervous system (epinephrine and norepinephrin e), a key piece in all these mechanisms of brain-immune communication. Poss ible mechanisms and pathways of communicatioin between the brain and the im mune system, as well as the possible participation of other cytokines are d iscussed.