IL-36 cytokines are increased in acne and hidradenitis suppurativa

Abstract

Interleukin (IL)-36 cytokines are new members of the IL-1 family, which include pro-inflammatory factors, IL-36α, IL-36β and IL-36γ, and a natural receptor antagonist IL-36Ra. Over recent years, much has been learned on their important functions in the regulation of immune response and, especially, on their role in many inflammatory skin diseases. However, to date, no data have been reported on their possible involvement in acne and hidradenitis suppurativa (HS). Here, we have shown that IL-36α, IL-36β, and IL-36γ are increased in lesional skin of acne and HS, highlighting their possible pathogenetic contribution to these two skin conditions. In contrast, IL-36Ra (the anti-inflammatory member of IL-36 sub-family) was increased just in psoriasis, suggesting that an imbalance in IL-36/IL36Ra functions could play a role in the phenotype of skin damage. One of the consequences of this imbalance may be the increased induction of IL-8 that we found higher in acne, HS, and ACD respect to psoriasis.

Upregulation of IL‐36 cytokines in folliculitis and eosinophilic pustular folliculitis

“…The levels of IL‐36 family members in keratinocytes are markedly increased by many different stimuli, including Toll‐like receptor (TLR) agonists such as bacterial lipopolysaccharide . The mRNA expression of IL‐36α, IL‐36β and IL‐36γ was previously reported to be elevated in lesional skin of acne . Our study showed that the protein expression of IL‐36β, IL‐36γ and IL‐36Ra was increased in the epidermis and follicular epithelial cells in folliculitis and EPF compared with the levels in normal skin.…”

“…7,8 The mRNA expression of IL-36a, IL-36b and IL-36c was previously reported to be elevated in lesional skin of acne. 14 Our study showed that the protein expression of IL-36b, IL-36c and IL-36Ra was increased in the epidermis and follicular epithelial cells in folliculitis and EPF compared with the levels in normal skin. IL-36 cytokines are secreted as precursor proteins with little or no bioactivity, so they require post-enzymatic processing to elicit their biological effects.…”

“…Loss‐of‐function mutations of IL36RN cause GPP, which is characterised by marked neutrophilic infiltration in the epidermis . The elevated IL‐36Ra in folliculitis and EPF might play a role in suppressing excessive IL‐36β and IL‐36γ activation …”

“…9,10,26 The elevated IL-36Ra in folliculitis and EPF might play a role in suppressing excessive IL-36b and IL-36c activation. 14 We examined the IL-36 expression in EPF, an eosinophilic inflammatory skin disease. Similar to folliculitis, high expression of IL-36b, IL-36c and IL-36Ra was detected in the follicular epithelium and epidermis in EPF compared with the levels in normal skin.…”

“…One of the major biological functions of IL‐36α, IL‐36β and IL‐36γ is their potent neutrophilic and eosinophilic chemoattraction . Therefore, the overexpression of IL‐36s has been documented in various skin diseases such as allergic contact dermatitis, atopic dermatitis, mycosis fungoides, Sézary syndrome, autoimmune blistering diseases, hidradenitis suppurativa and acne . Eosinophilic pustular folliculitis (EPF) is a distinct clinical entity first described in 1965 by Ise and Ofuji as a variant of superficial pustular dermatosis .…”