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Psoriasis affects approximately 2% of the Western population and about 123,000,000 persons worldwide. It is a disease characterized by chronic inflammatory skin lesions; however patients may also suffer from arthritis or even life-threatening, systemic inflammation. Treatments consist of topical emollients and steroids, as well as systemic therapies including immunosuppressive regimens and targeted biologics. The inciting lesion behind the pathogenesis of this disease is unknown, however it has increasingly become apparent that psoriasis is a complex, immune-mediated disease.
Raised, erythematous, scaly plaques characterize the psoriatic lesion. Microscopically, these plaques show hyperproliferative keratinocytes, neoangiogenesis, and inflammatory cell infiltration. And while it is unclear whether the primary genetic lesion in psoriasis is found in the epidermal keratinocyte or the bone marrow derived inflammatory cells, it is clear that cytokine production from both of these cell lines contributes to the pathogenesis of the disease.
Keratinocytes are large reservoirs for preformed, intracellular, and biologically active IL-1α. Excess IL-1 activity promotes the production of adhesion molecules by endothelial cells and release of chemokines, both of which lead to infiltration of the tissues by white blood cells. Once in the dermis, some of these white blood cells can differentiate into macrophages and dendritic cells, which can induce psoriatic skin changes through further production of proinflammatory cytokines. This cycle of inflammation and infiltration by white blood cells likely plays a significant role in the chronic inflammatory component of psoriasis.
Mouse models have been used to illustrate the importance of IL-1 in the development of psoriasis. Animals genetically lacking a single mechanism used to naturally regulate the effects of IL-1 spontaneously develop psoriasis-like disease. Interestingly, these mice also develop atherosclerosis- and arthritis-like disease.
Cutaneous inflammation, in terms of both macro and microscopic features, looks markedly like psoriatic lesions. Similar results have been seen in mice that are bred to over-express IL-1α in the skin. Mice that overproduce IL-1α in basal keratinocytes, develop sparse hair and fine, scaly skin. These mice often progress to develop inflammatory psoriatic-like skin lesions, which when healed, led to a scarred region devoid of hair. Other studies using human keratinocyte cultures show that IL-1α induces similar genetic changes compared to skin in subjects with psoriasis.
IL-1α is an extremely potent pro-inflammatory cytokine, which has long been associated with keratinocytes. Pre-clinical data has suggested that this cytokine may be involved in the pathogenesis of psoriasis, and a recent case study provides powerful evidence for this hypothesis.
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