Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis.
BACKGROUND
Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity.


OBJECTIVE
To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern.


METHODS
Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase-antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4.


RESULTS
The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN.


CONCLUSIONS
We have provided further evidence that TNF-alpha is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN-gamma may play an important role both in EM and SJS/TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.
Caproni
M
M
Department of Dermatological Sciences, University of Florence, Florence, Italy.
Torchia
D
D
Schincaglia
E
E
Volpi
W
W
Frezzolini
A
A
Schena
D
D
Marzano
A
A
Quaglino
P
P
De Simone
C
C
Parodi
A
A
Barletta
E
E
Fabbri
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism*; D004892:Erythema Multiforme / Q000276:immunology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D013262:Stevens-Johnson Syndrome / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C515350:CCR3 protein, human; C515187:CXCR3 protein, human; D016207:Cytokines; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine