Interleukin (IL) 31 induces in cynomolgus monkeys a rapid and intense itch response that can be inhibited by an IL‐31 neutralizing antibody

Abstract Background Overexpression or administration of interleukin 31 ( IL ‐31) has been shown to induce a profound itch response in mice and dogs. The chronic pruritus observed in mouse IL ‐31 transgenic mice results in the development of skin lesions and alopecia through excoriation from excessive scratching, a condition similar to that observed in patients with atopic dermatitis ( AD ). Objective To test whether IL ‐31 induces pruritus in non‐human primates and, if so, whether treatment with an anti‐ IL ‐31 neutralizing monoclonal antibody ( mA b) can block the response. Methods A series of studies was conducted in cynomolgus monkeys to evaluate the itch response to recombinant cynomolgus IL ‐31 ( cIL ‐31) administration. Three routes of cIL ‐31 administration (intravenous, intradermal, and subcutaneous) were evaluated. Subcutaneous treatment with a humanized anti‐human IL ‐31 mA b cross‐reactive to cIL ‐31 was subsequently tested for its ability to block the response to intradermal cIL ‐31 administration. Results Each route of cIL ‐31 delivery elicited a scratching response immediately after cIL ‐31 administration and lasted at least 3 h. Treatment with the IL ‐31 mA b inhibited the cIL ‐31‐mediated scratching response in a dose‐dependent manner. Conclusion These results demonstrate that an IL ‐31 mA b can inhibit IL ‐31‐mediated pruritus in vivo , and could be an effective therapy for pruritic skin conditions like AD where IL ‐31 upregulation may play a role.