Fibroblasts as Target and Effector Cells in Japanese Patients with Sarcoidosis

Fibroblasts play a crucial role in progressive lung fibrosis, acting not only as target cells but also as effector cells. To clarify these functions in sarcoidosis, lung fibroblasts from Japanese sarcoid patients were studied for their proliferative capacity and cytokine productivity. Fibroblasts were cultured from transbronchial lung biopsy specimens from seven patients with sarcoidosis. As a comparison, fibroblasts from open lung biopsy specimens of four patients with idiopathic pulmonary fibrosis (IPF) were studied. For controls, fibroblasts were cultured from specimens of normal resected lung tissue of five patients with localized lung cancer. The proliferative activity of cultured fibroblasts from patients with sarcoidosis was highest among the three groups (p < 0.05). However, the proliferative capacity in all groups was suppressed when fibroblasts were cultured with interleukin-1beta (IL-1beta). No significant differences were noted in the degree of inhibition among the three groups. Addition of interferon-gamma (IFN-gamma) also resulted in inhibition of fibroblast growth in all groups, but the degree of inhibition was significantly greater in both the sarcoid and IPF groups than in controls (p < 0.05). The amount of interleukin-6 (IL-6) in the culture supernatants from sarcoid fibroblasts cocultured with IL-1beta was significantly higher than in controls. Sarcoid fibroblasts are not only proliferatively active but also possess effector cell function to produce cytokines. IL-6 may enhance the immunologic reaction to sarcoidosis and cause the disease to become chronic. IFN-gamma suppresses proliferation of sarcoid fibroblasts and may prevent fibrotic changes of the lungs in the Japanese sarcoid patients.