title: 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 (mAb) 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 mAb 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 mAb inhibited the cIL-31-mediated scratching response in a dose-dependent manner.
  
  
  CONCLUSIONS
  These results demonstrate that an IL-31 mAb 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.
authors: Discovery Biology Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: K E
authors: KE
authors: Lewis
authors: Preclinical Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: M S
authors: MS
authors: Holdren
authors: Discovery Biology Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: M F
authors: MF
authors: Maurer
authors: Preclinical Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: S
authors: S
authors: Underwood
authors: Protein Engineering Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: B
authors: B
authors: Meengs
authors: Protein Engineering Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: S H
authors: SH
authors: Julien
authors: Preclinical Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: K A
authors: KA
authors: Byrnes-Blake
authors: Preclinical Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: J A
authors: JA
authors: Freeman
authors: Bioprocess Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: T R
authors: TR
authors: Bukowski
authors: Bioprocess Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: A C
authors: AC
authors: Wolf
authors: Bioprocess Development Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: N B
authors: NB
authors: Hamacher
authors: Protein Engineering Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: M W
authors: MW
authors: Rixon
authors: Discovery Biology Group, ZymoGenetics Inc. (a Bristol-Myers Squibb Company), Seattle, WA, USA.
authors: S R
authors: SR
authors: Dillon
mesh_terms: D000818:Animals; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage* / Q000276:immunology; D008252:Macaca fascicularis; D051379:Mice; D009500:Neutralization Tests
chemical_list: D007378:Interleukins; C502588:interleukin-31, mouse