The immunopathophysiology of psoriasis : studies on accessory cells, cytokines and their receptors

textabstractThe above data show that prodigious alterations occur in the expression of cytokines and their receptors in psoriasis. Although a crucial role lor cytokines in the pathogenesis is almost definite, the results do not unequivocally demonstrate a primary cytokine defect in psoriasis. Furthermore, the data described are often contradictory. This may be caused by the use of different skin specimens, the detection of cytokines and receptors at different levels (eg. transcription, protein and bioactivity) combined with the use of different detection techniques. Despite the fact that data on cytokines in normal and psoriatic skin is far from complete, several alterations in psoriasis are evident: 1) dysregulation of IL-1; 2) increased levels of IL-6, IFN--y and especially IL-8 and TGF-a; 3) altered responsiveness of keratinocytes to IFN--y; and finally; 4) clearly increased expression of the EGFjTGF-a receptor. Taking these findings into account, psoriasis may be considered a multi-factorial immunological disease in genetically predisposed individuals with primary defect(s), probably residing in the cutaneous signalling system. A specifically altered cytokine profile in association with an altered response of the keratinocytes to these cytokines links inflammation with the hyperactive state in the epidermis in psoriasis. It is conceivable that this deviant cutaneous signalling system plays a central role in the pathogenesis of psoriasis. The aims of our studies were to further delineate the basic abnormalities in skin APC and the cutaneous cytokine network in psoriasis. The experimental work on APC, cytokines and cytokine receptors in the psoriatic skin are described in Chapters 3 to 7. In Chapter 8, the implications of our findings are discussed in the context of the literature data on the altered cytokine network in psoriasis