Ultrastructural Findings and Tumor Necrosis Factor-alpha and Intercellular Adhesion Molecule-1 Expression in Psoriasis Patients Before and After Oral Cyclosporin A Therapy

Abstract

Elevated levels of proinflammatory cytokines, including tumor necrosis factor-alpha, are found in skin lesions and plasma of patients with psoriasis. Clinical improvement of psoriasis with cyclosporin A treatment is accompanied by downmodulation of proinflammatory epidermal cytokines. In this study to determine the effects of cyclosporin A on the ultrastructural changes and tumor necrosis factor-alpha and intercellular adhesion molecule-1 expression in psoriasis, biopsy specimens before and after cyclosporin A treatment were evaluated ultrastructurally and immunohistochemically. Ten patients were given 3-7.5 mg/kg oral cyclosporin A for 6 months. Before and after treatment full thickness of 4-mm punch biopsies were obtained from patients and from 6 healthy volunteers. Samples were processed for electron microscopic and immunohistochemical evaluation. The treatment was well tolerated with complete clinical improvement. The ultrastructural changes such as reduction of tonofilaments, dilatation of intercellular space, and interruption in lamina densa were recovered by cyclosporin A treatment. The increased staining intensity of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on epidermal keratinocytes and endothelial cells was reduced after cyclosporin A therapy. Cyclosporin A treatment results in total normalization of the electron microscopic picture of psoriasis and its beneficial effect depends on the direct inhibition of tumor necrosis factor-alpha and consequently intercellular adhesion molecule-1.

Expression of the T‐cell‐specific adapter protein in oral epithelium

“…The blistering and the breach in continuity in the BM observed in the present study, closely resemble ultrastructural changes that can be observed in the skin of patients with lupus erythematosus and in the skin of a mouse model of systemic lupus erythematosus (SLE) (MRL/l strain) (35)(36)(37)(38). Furthermore, in psoriatic skin lesions, the lamina densa can be interrupted, as observed in the SH2D2A )/) mice in the present study (39). In oral lichen planus, disturbances of the basal lamina, such as increased width of the lamina densa and loss of hemidesmosomes, can be seen (40,41).…”

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

“…Vessels were highly aberrant in the dermis of psoriatic skin 22 , 23 . Some researchers have proved that E-selectin CD54 and CD106 are over expressed in inflamed vasculature in psoriatic lesions 24 , 25 . In our experiment, in contrast with the pIL-4-DMSO application formula without RA, more significant reductions of the expression of these cell adhesion molecules were presented in the formula using RA-pIL-4-DMSO ( Fig.…”

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

“…Additional pharmacotranscriptomic approaches in the CsA treatment revealed the molecular reversion of several cytokine levels [ 58 , 59 ] and transforming growth factor (TGF)-β isoforms [ 60 ], with the former study further displaying the reduction of K16 + , CD3 + , and CD25 + cells in the lesional skin [ 58 ]. Furthermore, immunohistochemical staining for TNF and ICAM-1 of psoriatic skin was significantly reduced after CsA treatment approaching non-lesional levels [ 61 ].…”