Cytokine profile and supposed contribution to scarring in cicatricial pemphigoid.
BACKGROUND
The progressive scarring observed in cicatricial pemphigoid (CP) is still partially unexplained but recently the release of soluble fibrogenic factors by inflammatory infiltrating cells has been considered as pathogenically relevant. In the present study we evaluated the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in CP in comparison to bullous pemphigoid (BP) patients, investigating the role of cytokine profile as possible cause of the different disease evolution.


METHODS
Biopsies from patients with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied by in situ hybridisation performing a new amplification system based on biotinyl-tyramide. As control, four patients affected by BP were also examined, together with healthy tissue from two CP and two BP patients, respectively.


RESULTS
In CP IL-4 mRNA expression was present in 4 out of 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, IL-4 hybridisation signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all BP cases. Healthy specimens did not show any expression for IL-4, IL-5 and IFN-gamma, while a poor staining for TGF-beta was found in epithelium and subjunctional areas.


CONCLUSIONS
Our results highlight the presence of a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP suggest that the involvement of additional factors is responsible for the scarring course typical of CP.
Caproni
Marzia
M
Department of Dermatological Sciences, University of Florence, Italy. fabbri@unifi.it
Calzolari
Anna
A
Salvatore
Elisabetta
E
Giomi
Barbara
B
Volpi
Walter
W
D'Agata
Alberino
A
Santucci
Marco
M
Fabbri
Paolo
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002921:Cicatrix / Q000209:etiology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D015848:Interleukin-5 / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000276:immunology / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism; D010390:Pemphigoid, Benign Mucous Membrane / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D010391:Pemphigoid, Bullous / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma