Physiological role of the IL-1 family cytokines and receptors in the human brain

Cytokines and receptors of the IL-1 family are generally known for their role in inducing and modulating the inflammatory responses upon infectious challenges and, in particular, for their pathological role in chronic inflammatory, degenerative and autoimmune diseases. On the other hand, increasing evidence supports the notion that these molecules have a physiological role in promoting and maintaining tissue homeostasis in normal healthy conditions. The physiological importance of IL-1 family cytokines and receptors in the human brain is of particular interest, since several of these molecules are preferentially or specifically expressed in the brain and absent in other body compartments. Here, we critically examine the evidence pointing at the homeostatic functions of IL-1 family members in the human healthy brain, and highlight the existence of multiple/alternative mechanisms of brain cell regulation initiated by these molecules, including neurogenesis and neurodevelopment, neuroplasticity, neuroendocrine and neurometabolic functions.