POSSIBLE INVOLVEMENT OF INTERLEUKIN-1 IN THE PATHOGENESIS OF DERMATOFIBROMA

Dermatofibroma (DF) is histologically characterized by proliferation o f fibroblasts in the dermis. Multiple DFs occasionally develop in pati ents with autoimmune disorders under immuno-suppressive therapy; howev er, the pathogenesis of DF is still unclear. To elucidate immunologica l involvement in the mechanism of the fibrosis in DF,,ve studied the r ole of interleukin-1 (IL-1), which has a number of biological function s, including proliferation and collagen production of fibroblasts, on DF-derived fibroblasts. H-3-thymidine incorporation was used to examin e the effects of IL-1 alpha and IL-1 beta in 4 cultured fibroblast str ains derived from DF and 5 fibroblast strains from normal skin. Expres sion of mRNA of IL-1 was also analyzed by reverse transcriptase polyme rase chain reaction (RT-PCR). Basal H-3-TdR incorporation without stim ulant of DE-derived fibroblasts showed a significantly greater growth activity than normal skin-derived fibroblasts (2, 632 +/- 525 vs. 762 +/- 144 dpm, p < 0.01). Both IL-1 alpha and IL-1 beta showed a stronge r growth-stimulatory activity on DE-derived fibroblasts in a dose-depe ndent manner than normal fibroblasts, and the percent 3H-TdR uptake of DF was 1.4-fold (IL-1 alpha; 1,000 U/ml) and 1.3-fold (LL-1 beta; 1,0 00 U/ml) as compared with normal fibroblasts; however, the differences did not reach any significance. When increasing concentrations of IL- 1 receptor antagonist (IL-1ra) were added to culture medium stimulated with IL-1 alpha, the proliferative response of fibroblasts,vas signif icantly reduced. Expression of IL-1 beta mRNA was detected on both DF- derived and normal skin-derived fibroblasts, while that of IL-1 alpha mRNA was detected only on DF-derived fibroblasts. Our results suggest that IL-1 may be involved in the fibrotic process in DF at the transcr iptional level and play a role in the fibroblast proliferation in an a utocrine manner.