A new T helper 17 cytokine in hidradenitis suppurativa: antimicrobial and proinflammatory role of interleukin-26.

BACKGROUND: Interleukin (IL)-26 is a signature T helper 17 cytokine described as a proinflammatory and antimicrobial mediator. So far, IL-26 has been reported in several immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders is poorly known. OBJECTIVES: To investigate the role of IL-26 in hidradenitis suppurativa (HS), through its involvement in antimicrobial activity. METHODS: IL-26 was assessed in patients with HS through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL-26 antibody treatment, were performed to determine the IL-26 activity. Peripheral blood mononuclear cells (PBMCs) from patients with HS and healthy controls were either silenced or not with IL-26 small interfering (si)RNA in order to measure its antimicrobial, cytotoxic and phagocytic activities against Staphylococcus aureus. RESULTS: Firstly, we observed that IL-26 is able to modulate the proinflammatory response at the immune cell level. IL-26 was increased in the plasma of patients with HS compared with healthy controls. Subsequently, we explored the bactericidal, cytotoxic and phagocytic activities of PBMCs against S. aureus in patients with HS and healthy controls. These activities were lower in patients with HS than in controls. Remarkably, the killing activities were reduced when healthy control PBMCs were transfected with IL-26 siRNA. However, the transfection did not affect the killing activity of HS PBMCs, supporting the idea that IL-26 lacks efficacy in HS. CONCLUSIONS: Our findings suggest that infection susceptibility in HS might be related to IL-26. Although the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. What's already known about this topic? Interleukin (IL)-26 is a T helper 17 cytokine described as an antimicrobial and proinflammatory mediator. IL-26 has been reported in immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders remains unclear. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by deficiency of IL-20 and IL-22 (a close homologue of IL-26), which causes antimicrobial peptide pauperization leading to severe and recurrent skin infections. What does this study add? IL-26 plasma levels are higher in patients with HS than in healthy control individuals. The antimicrobial activity of IL-26 might be ineffective in patients with HS. What is the translational message? Cutaneous antimicrobial incompetence in HS could be related to IL-26.

Understanding the role of haptoglobin in psoriasis: effects of ultraviolet B.

BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main function is to bind free haemoglobin (Hb) and transport it to the liver for degradation and iron recycling. In addition to its role as an Hb scavenger, Hp has been shown to behave as an anti-inflammatory, antioxidant and angiogenic factor. We previously investigated the role of Hp in the pathogenesis of psoriasis, and found that it displays some structural modifications that might be associated with protein function in the disease. Phototherapy is an efficacious treatment for psoriasis, although the biological mechanisms by which phototherapy improves psoriasis are still unclear. AIM: To investigate the effects of ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS: Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp gene and protein expression in the skin of patients with psoriasis was also investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10 gene expression and Hp gene and protein expression in HaCaT cells. The in vivo data also showed that Hp levels were increased in the skin of patients with psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able to modulate Hp production in immortalized keratinocytes. The higher levels of Hp in vivo in both lesional and nonlesional skin suggest that it might have a role in the pathogenesis of the disease.

Effects of adalimumab therapy in adult subjects with moderate-to-severe psoriasis on Th17 pathway.

BACKGROUND: Until relatively recently, psoriasis has been considered to be a mainly T helper (Th)1-driven inflammatory disease; however, several findings have now assessed a major role for Th17 cells in its pathogenesis. Adalimumab is a biological agent that inhibits TNF-α, a pro-inflammatory cytokine with a pivotal role in the mechanisms of the disease. OBJECTIVE: To elucidate the in vivo effects of adalimumab therapy on Th17 pathway. METHODS: Quantitative real-time reverse transcriptase polymerase chain reaction was used to analyse levels of expression of Th17 polarizing cytokines (IL-23A, TGF-ß, IL-1ß, IL-6), Th17 cytokines (IL-17, IL-22) as well as TNF-α, Th1 polarizing cytokine (IFN-α) and Th17 downstream effector mediators, such as chemokines (IL-8, CCL-20) in skin and peripheral blood mononuclear cells before and after 16 weeks of adalimumab therapy. Similarly, gene expression of Th17 induced mediators by keratinocytes (antimicrobial peptides: HBD-2, S100A7) was investigated at skin level. In addition, cutaneous and plasma IL-17 was examined by immunohistochemistry and enzyme-linked immunosorbent assay respectively. Efficacy of the treatment was assessed by several clinical index scores as well as epidermal thickness reduction. RESULTS: Adalimumab therapy led to improvement in skin disease scores in all patients. Moreover, adalimumab treatment down-modulated Th17 pathway at skin level. Plasma IL-17 levels and IL-17-positive cells in psoriatic lesional skin were decreased by adalimumab treatment. CONCLUSIONS: Our data highlight that the immunomodulatory activity of adalimumab is associated with considerable clinical improvements as well as a potent shut down of Th17 response in patients with moderate-to-severe psoriasis.