BACKGROUND AND PURPOSEIL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined.
EXPERIMENTAL APPROACHWe investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype.
KEY RESULTSThe scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a μ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed.
CONCLUSIONS AND IMPLICATIONSAnti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch-scratch cycle and also a treatment for dermatitis in AD.
AbbreviationsAb, antibody; AD, atopic dermatitis; CS, contact sensitivity; OSMR, oncostatin M receptor; PiCl, picryl chloride; Th2, T helper 2 Table lists key protein targets and ligands in this document, which are hyperlinked to corresponding entries in http:// www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14 (Alexander et al., 2013a.
BJP
IntroductionAtopic dermatitis (AD) is a chronic, highly pruritic and inflammatory skin disease characterized by disease exacerbations and remission. In AD, a major diagnostic criterion that impairs the patient's quality of life is persistent pruritus (Williams et al., 1994;Hanifin, 1999), which is also a cause of a more severe phenotype known as the itch-scratch cycle. In the itchscratch cycle the strong actions of scratching facilitate both the susceptibility to increased itching and the exacerbation of skin lesions in patients with AD (Koblenzer, 1999;Stander and Steinhoff, 2002). Therefore, to escape from this vicious cycle by reducing the itching is crucial for preventing this aggravation of skin lesions and for improving the quality of life of patients with AD (Finlay, 2001;Greaves and Khalifa, 2004). The mediators that induce chronic scratching behaviour have not been fully characterized, and remedies for persistent pruritus have no...