Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis

Abstract

Background -Interleukin-31 (IL-31) is a member of the gp130 ⁄ interleukin-6 cytokine family that is produced by cell types such as T helper 2 lymphocytes and cutaneous lymphocyte antigen positive skin homing T cells. When overexpressed in transgenic mice, IL-31 induces severe pruritus, alopecia and skin lesions. In humans, IL-31 serum levels correlate with the severity of atopic dermatitis in adults and children.Hypothesis ⁄ Objective -To determine the role of IL-31 in canine pruritus and naturally occurring canine atopic dermatitis (AD).Animals -Purpose-bred beagle dogs were used for laboratory studies. Serum samples were obtained from laboratory animals, nondiseased client-owned dogs and client-owned dogs diagnosed with naturally occurring AD.Methods -Purpose-bred beagle dogs were administered canine interleukin-31 (cIL-31) via several routes (intravenous, subcutaneous or intradermal), and pruritic behaviour was observed ⁄ quantified via video monitoring. Quantitative immunoassay techniques were employed to measure serum levels of cIL-31 in dogs.Results -Injection of cIL-31 into laboratory beagle dogs caused transient episodes of pruritic behaviour regardless of the route of administration. When evaluated over a 2 h period, dogs receiving cIL-31 exhibited a significant increase in pruritic behaviour compared with dogs that received placebo. In addition, cIL-31 levels were detectable in 57% of dogs with naturally occurring AD ( ‡13 pg ⁄ mL) but were below limits of quantification (<13 pg ⁄ mL) in normal, nondiseased laboratory or client-owned animals.Conclusions -Canine IL-31 induced pruritic behaviours in dogs. Canine IL-31 was detected in the majority of dogs with naturally occurring AD, suggesting that this cytokine may play an important role in pruritic allergic skin conditions, such as atopic dermatitis, in this species.

IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function

“…IL-31-driven signaling has been shown to regulate a wide range of biological functions, including itch, induction of proinflammatory cytokines, regulation of cell proliferation, and tissue remodeling [3, 6, 7]. Previous studies have shown that IL-31 induces pruritus and severe dermatitis, and also regulates other allergic diseases that are characterized by these skin disorders [1, 8, 9]. Overexpression or administration of recombinant mouse IL-31 (rIL-31) in mice triggered a skin phenotype that in many ways resembled atopic dermatitis (AD) [1].…”

New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?

“…IL-31 mRNA is significantly up-regulated in serum and skin of patients with pruritic atopic dermatitis [39;141;147]. Canine IL-31 was also detected in the majority of dogs with naturally occurring atopic dermatitis and intradermal injection of it induced pruritic behaviors in dogs [46]. Higher levels of blood β-endorphin and IL-31 significantly correlated itch severity in atopic dermatitis patients [83].…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…When overexpressed in transgenic mice, IL-31 induces a pruritic skin condition that resembles human atopic dermatitis (Dillon et al, 2004). Importantly, T H 2 cells overproduce IL-31 in both canine (Gonzales et al, 2013) and human (Sonkoly et al, 2006) atopic dermatitis. A large subset of sensory neurons that coexpress TRPV1 with TRPA1 carry a receptor for IL-31 ; indeed, the IL-31-induced pruritus is ameliorated in both TRPV1-and TRPA1-deficient mice.…”

“…IL-31 produced by T H 2 cells evokes itch when injected into the skin of mice (Dillon et al, 2004) or dogs (Gonzales et al, 2013). Several lines of experimental evidence point to IL-31 as a critical neuroimmune link between pathogenic T cells and pruriceptive afferents.…”