Possible involvement of interleukin-1 in the pathogenesis of dermatofibroma

Dermatofibroma (DF) is histologically characterized by proliferation of fibroblasts in the dermis. Multiple DFs occasionally develop in patients with autoimmune disorders under immunosuppressive therapy; however, the pathogenesis of DF is still unclear. To elucidate immunological involvement in the mechanism of the fibrosis in DF, we studied the role of interleukin-1 (IL-1), which has a number of biological functions, including proliferation and collagen production of fibroblasts, on DF-derived fibroblasts. 3H-thymidine incorporation was used to examine the effects of Il-1 alpha and IL-1 beta in 4 cultured fibroblast strains derived from DF and 5 fibroblast strains from normal skin. Expression of mRNA of IL-1 was also analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). Basal 3H-TdR incorporation without stimulant of DF-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 stronger growth-stimulatory activity on DF-derived fibroblasts in a dose-dependent 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 (IL-1 beta; 1,000 U/ml) as compared with normal fibroblasts; however, the differences did not reach any significance. When increasing concentrations of IL-1 receptor antagonist (IL-1 alpha) were added to culture medium stimulated with IL-1 alpha, the proliferative response of fibroblasts was significantly reduced. Expression of IL-1 beta and RNA 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 transcriptional level and play a role in the fibroblast proliferation in an autocrine manner.