ALVEOLAR MACROPHAGES FROM PATIENTS WITH BERYLLIUM DISEASE AND SARCOIDOSIS EXPRESS INCREASED LEVELS OF MESSENGER-RNA FOR TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 BUT NOT INTERLEUKIN-1-BETA

Recent evidence suggests that the alveolar macrophage-derived cytokine s tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta ), and interleukin-6 (IL-6) play important roles in granulomatous dise ases. Our objective was to quantify the mRNA for these cytokines in be ryllium disease, a human granulomatous disease of known etiology. We h ypothesized that alveolar macrophages and bronchoalveolar lavage fluid from patients with beryllium disease and sarcoidosis would express in creased levels of mRNA and proteins, respectively, for TNF-alpha, IL-1 beta, and IL-6 compared with those of normal individuals. We performed bronchoalveolar lavage and used a quantitative polymerase chain react ion to determine alveolar macrophage-derived cytokine gene expression. We determined lavage fluid cytokine levels by enzyme-linked immunosor bent assay. In patients with beryllium disease (n = 23), we observed e levated macrophage mRNA expression for TNF-alpha and IL-6 when compare d with that of normal subjects (n = 7). Sarcoidosis patients (n = 6) a lso had increased expression for TNF-alpha and IL-6 compared with that of normal volunteers. IL-1beta expression was similar in all three gr oups. In patients with beryllium disease (n = 39), lavage fluid TNF-al pha concentration was higher than that of 16 normal subjects. Lavage f luid IL-1beta and IL-6 levels did not differ among the groups. This is the first report of macrophage cytokine expression in beryllium disea se. These novel findings suggest that macrophage expression of TNF-alp ha and IL-6 may be important in the human granulomatous inflammatory r esponse.