Role of cytokines and chemokines in itch.

Cytokines classically are secreted "messenger" proteins that modulate cellular function of immune cells. Chemokines attract immune cells to the site where they exert various functions in inflammation, autoimmunity or cancer. Increasing evidence is emerging that cytokines or chemokines can act as "neuro-modulators" by activating high-affinity receptors on peripheral or central neurons, microglia cells or Schwann cells. Very recently, cytokines have been shown to act as pruritogens in rodents and humans, while a role of chemokines in itch has thus far been only demonstrated in mice. Upon stimulation, cytokines are released by skin or immune cells and form a "bridge of communication" between the immune and nervous system. For some cytokines such as IL-31 and TSLP, the evidence for this role is strong in rodents. For cytokines such as IL-4, there is some convincing evidence, while for cytokines such as oncostatin M, IL-2, IL-6, IL-8 and IL-13, direct evidence is currently limited. Current clinical trials support the idea that cytokines and chemokines and their receptors or signalling pathways are promising targets for the future therapy of certain subtypes of itch.