FROM THE BLOOD- BRAIN BARRIER TO BEHAVIOR

Abstract

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 circumven- tricular organs. The affective and behavioural changes that develop during in- fluenza 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 recep-tor 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 infec- tious 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 disea- ses with an inflammatory component (cad, immunorheumatolic, neuropathologies (Cleeland 2003, Eikelenboom 2002, Gidron 2002, Kiecolt-Glaser and glaser 2002). These non-specific neurovegetative and psychiatric symptoms represent just another facet of the ingflammatory process and they are not necessarily derived from a direct cause-effect chain.