Exp Dermatol 1998: 7: 157–161 Copyright C Munksgaard 1998 Printed in Denmark ¡ All rights reserved ISSN 0906-6705 Decreased Interleukin-7 and transforming growth factor-beta 1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid Opposite behavior of TNF-alpha, Interleukin-4 and Interleukin-10 Giacalone B, D’Auria L, Bonifati C, Ferraro C, Riccardi E, Mussi A, B. Giacalone 1 , L. D’Auria 1,2 , D’Agosto G, Cordiali-Fei P, Ameglio F. Decreased Interleukin-7 and trans- C. Bonifati 1,2 , C. Ferraro 1 , forming growth factor-beta 1 levels in blister fluids as compared to the E. Riccardi 1 , A. Mussi 1,2 , respective serum levels in patients with bullous pemphigoid. Opposite G. D’Agosto 2 , P. Cordiali-Fei 2 behavior of TNF-alpha, Interleukin-4 and Interleukin-10 and F. Ameglio 2 Exp Dermatol 1998: 7: 157–161. C Munksgaard, 1998 1 Division of Dermatology, 2 Laboratory of Clinical Pathology, San Gallicano Institute, IRCCS, Rome, Abstract: This study analyzes both the blister fluid (BF) and serum levels Italy of IL-7 and TGF-beta 1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P∞0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no signifi- cant TGF-beta 1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (rΩ0.64, PΩ0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (rΩ0.80, P∞0.001) and anti- bodies directed against the basement membrane zone (rΩ0.65, P∞0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at Key words: blister fluid – bullous pemphigoid – the local level (keratinocyte is known to produce IL-7 and the latter is IL-4 – IL-7 – TGF-b 1 – TNF-a – serum known to be down-regulated by IL-10, and in other models also by TGF-beta 1 and IL-4, whose levels are elevated in BP BFs) as opposed to Franco Ameglio, M.D., Istituto S. Gallicano, Via S. Gallicano 25/A, 00153 Roma, Italy an increased peripheral release of the same modulator. The IL-7 reduc- Fax: ππ39-6-58543747 tion may have a biological relevance in controlling a chronic, progressive disease. Accepted for publication 13 January 1998 Introduction Because of their general involvement in cell regula- tion, cytokines are widely studied in many derma- tologic diseases (1), including bullous pemphigoid (BP) (2, 3), an autoimmune disease based on speci- fic anti-basement membrane zone antibodies. This rare disease (prevalence ranges between 0.1 and 1 case/100,000 individuals) characterized by blister formation leading to erosions, shows an evi- dent inflammatory component, confirmed by sig- 157 nificant increases in the blister fluids (BFs) of several cytokines as compared to serum concentrations (in- terleukin-1b, interleukin-2, interleukin-3, interleu- kin-4 [IL-4], interleukin-5, interleukin-6, interleu- kin-8, interleukin-10 [IL-10], interleukin-12, inter- feron-gamma and tumor necrosis factor-alpha [TNF-alpha]) as reported in the literature (4, 5). In contrast, this study reports that the BF in- terleukin-7 (IL-7) and the transforming growth factor-beta 1 (TGF-beta 1 ) levels were lower than those observed in the sera.