FROM THE BLOOD- BRAIN BARRIER TO BEHAVIOR

Research in the field of neuropsychoimmunology has enabled the researchers to show that cytokines target the brain to organize a "sickness response," which is fever, activation of hypothalamuspituitary -adrenal axis and behavioural alterations that develop in sick individuals. Perypheral cytokines do not act directly on the brain; they trigger the production of cytokines in the brain parenchima itself, with a possible relay at the interface between internal milieeu and the brain, which are endothelial cells and circumventricular organs. The affective and behavioural changes that develop during influenza are the product of a transient brain inflammatory response induced by the same proinflammatory cytokines that are produced in the bronchial tree. The cytokine pattern is distal to this phenomenon while the receptor molecules that decipher the molecular nature of microbial pathogens (pathogens associated molecular patterns PAMPs) at the membrane level of cells is a proximal factor. PAMPs are recognized by specialized receptors on innate immune cells that belong to the TOLL/ IL-1 like receptor family. These receptors are phylogenetically old. the brain uses these receptors to defend itself against something different (several forms of brain injury that have nothing to do with infectious pathogens) from infectious pathogens. Assuming that the factors that activate these receptors involve endogenous substances derived by cell death (cell death by-products) is the concept at the origin of the danger theory. Evidence in favor of a citokines role in mediating mood disorders and cognitive disturbances in patients receiving cytokine immunotherapy is fast growing (capuron e dantzer 2003). Several items of data support the role for cytokines in mediating a variety of non -specific symptoms that develop in patients suffering from diseases with an inflammatory component (cad, immunorheumatolic, neuropathologies). These non-specific neurovegetative and psychiatric symptoms represent just another facet of the inflammatory process and they are not necessarily derived from a direct causeeffect chain.