Bidirectional interdependence between the immune system and the CNS involves the intervention of common cofactors. Cytokines are endogenous to the brain, endocrine and immune systems. These shared ligands are used as a chemical language for communication. Such interaction suggests an immunoregulatory role for the brain, and a sensory function for the immune system. Interplay between the immune, nervous and endocrine systems is associated with effects of stress on immunity. Cytokines are thus capable of modulating responses in the CNS, while neuropeptides can exert their effects over cellular groups in the immune system. One way is controlled by the HPA axis, a coordinator of neuroimmune interactions that is essential to unravel in order to elucidate vital communications in a manner that this crosstalk remains a cornerstone in perpetuating a stance of homeostasis. (c) 2008 Elsevier Inc. All rights reserved.