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-β, IL-1β, 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.
© 2013 European Academy of Dermatology and Venereology.