Production of cytokines in sarcoid lymph nodes: Preferential expression of interleukin-1β and interferon-γ genes

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-2, and interferon-γ (IFN-γ) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1β gene was preferentially expressed. The distribution of cells containing IL-1β mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-α gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1α gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1β gene was significantly higher than that of cells expressing TNF-α gene ( P = .001), IL-6 gene ( P = .007), or IL-1α gene ( P < .001). Of the cells expressing lymphokine genes, those expressing the IFN-γ gene were 31.9 (±7.6) times more frequent than those expressing the IL-2 gene ( P < .001). Cells containing IFN-γ mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1β gene and the IFN-γ gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.