Jak Inhibition May Ameliorate Pruritus Save

Last week we reported the results of a metanalysis published in the Journal of Investigative Dermatology showing that certain agents are more effective in managing the pruritus of psoriasis, including the inhibitors of IL-17, Janus kinase (Jak), adalimumab and apremilast. (https://buff.ly/2j3Oq9I)

Further credence to the effects of Jak inhibition are found in a report from Cell, where researchers from the Dermatology division at the Washington University School of Medicine have examined the role of type 2 cytokines in the activation of sensory neurons that may be involved in pruritus.  

They note that clinical studies demonstrate that JAK inhibitors relieve chronic itching. The current report details five patients with chronic idiopathic pruritus who improved when given tofacitinib. Earlier treatment with other anti-inflammatory drugs failed to help their chronic itching, but within one month of taking tofacitinib, all five patients reported marked relief from severe itching.

These researchers showed that sensory neurons in mice and humans are activated by the type 2 cytokine, interleukin-4 (IL-4). They also showed IL-4 enhances neuronal responsiveness to multiple pruritogens and that sensory neuron-specific deletion of IL-4Rα or JAK1 reduces chronic itch.

The authors believe, "This study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior."