Cytokine mRNA gene expression in active and nonactive pulmonary sarcoidosis

Sarcoidosis is a multisystem granulomatous disease associated with the expansion and activation of CD4+ T-lymphocytes and macrophages. To investigate the immunopathology of active and nonactive pulmonary sarcoidosis, we have examined the expression of cytokine gene transcripts in bronchoalveolar lavage cells from 15 patients with active pulmonary sarcoidosis, eight patients with non-active pulmonary sarcoidosis, and nine normal controls. Using in situ hybridization, the percentage of cells expressing messenger ribonucleic acid (mRNA) for interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) were compared in the groups studied. In individuals with active sarcoidosis, there were significantly greater proportions of cells expressing mRNA for IL-2, IL-10, IL-12 and IFN-gamma than in subjects with nonactive disease and normal controls (p < 0.01). There was no significant difference in the percentage of positive cells expressing IL-10 and IL-12 mRNA in the nonactive group compared to the normal controls (p > 0.05). No significant differences in the percentages of IL-3, IL-4 and IL-5 mRNA positive cells were observed between active and nonactive sarcoidosis patients and normal controls (p > 0.05). These results demonstrate that there is a preferential expression of T-helper type 1 cytokines in pulmonary sarcoidosis, and that cytokines related to macrophage activation are the most prominent. In addition, these data implicate an elevated expression of interleukin-2, -10 and -12 and interferon-gamma in active compared to nonactive sarcoidosis.