1. Departments of Dermatology, University ''G.D'Annunzio'', Chieti, Italy
2. ^*University of Ancona, Ancona, Italy
3. ^†Catholic University, Rome, Italy
4. ^‡Sunnybrook HSC, University of Toronto, Toronto, Canada

Correspondence: Dr Claudio Feliciani, Clinica Dermatologica, Via dei Vestini, 66013 Chieti, Italy. Email: feliciani@unich.it

Received 12 February 1999; Revised 31 August 1999; Accepted 20 September 1999.

Abstract

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1 and tumor necrosis factor-, in lesional and perilesional areas. Results were confirmed by reverse transcriptase–polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1 and tumor necrosis factor- mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1 and tumor necrosis factor- in keratinocytes cultures. A combination of anti-interleukin-1 and anti-tumor necrosis factor- antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor- in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE–/–, interleukin-1–/–) and tumor necrosis factor- receptor deficient mice (TNFR1R2–/–). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor- in the pathogenesis of pemphigus vulgaris.