INTRODUCTION
Psoriasis is a chronic, inflammatory, immune-mediated systemic disease with an estimated prevalence of 3.2% in the United States among individuals >20 years of age.1 It is characterized by abnormal proliferation of keratinocytes, increased dermal vascularity, and dermal infiltration of multiple inflammatory cells and by clinical presentation of erythema, induration, and scaling.2,3 Psoriasis has multiple symptoms with a substantial effect on both physical and emotional health-related quality of life, as well as a number of comorbid conditions.4-6
A complex series of immunologic events results in the formation of psoriatic plaques as well as the underlying systemic inflammation characteristic of psoriasis. Central to this process is the keratinocyte activation of dendritic cells. Inflammatory dendritic cells release interleukin-23 (IL-23) and IL-12 to activate helper T (Th17) cells, Th1 cells, and Th22 cells, which in turn produce psoriatic cytokines, including IL-17, tumor necrosis factor α (TNFα), and IL-22.7-9 The initial causes (environmental and/or genetic) that trigger the aberrant immune response and resulting cascade of immunologic events in psoriasis pathology are still not completely defined.
The current understanding of the complex pathophysiology associated with psoriasis has spurred the development of a variety of important new therapeutic agents that selectively target proinflammatory cytokines (eg, IL-17, IL-23, TNFα) rather than suppressing the immune system in its entirety, resulting in favorable efficacy and safety profiles compared with those of less-selective immunosuppressive agents.3 This review focuses on the central role of the IL-17 pathway in psoriasis pathophysiology and the clinical and molecular effects of the blockade of this pathway in the context of psoriasis treatment.
Overview of the Central Role of the IL-17 Pathway in Psoriasis
For many years, the Th1 pathway had been considered the primary driver in psoriasis.10 Research over the last decade,
A complex series of immunologic events results in the formation of psoriatic plaques as well as the underlying systemic inflammation characteristic of psoriasis. Central to this process is the keratinocyte activation of dendritic cells. Inflammatory dendritic cells release interleukin-23 (IL-23) and IL-12 to activate helper T (Th17) cells, Th1 cells, and Th22 cells, which in turn produce psoriatic cytokines, including IL-17, tumor necrosis factor α (TNFα), and IL-22.7-9 The initial causes (environmental and/or genetic) that trigger the aberrant immune response and resulting cascade of immunologic events in psoriasis pathology are still not completely defined.
The current understanding of the complex pathophysiology associated with psoriasis has spurred the development of a variety of important new therapeutic agents that selectively target proinflammatory cytokines (eg, IL-17, IL-23, TNFα) rather than suppressing the immune system in its entirety, resulting in favorable efficacy and safety profiles compared with those of less-selective immunosuppressive agents.3 This review focuses on the central role of the IL-17 pathway in psoriasis pathophysiology and the clinical and molecular effects of the blockade of this pathway in the context of psoriasis treatment.
Overview of the Central Role of the IL-17 Pathway in Psoriasis
For many years, the Th1 pathway had been considered the primary driver in psoriasis.10 Research over the last decade,
