INCREASED SECRETION OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-1-BETA, AND INTERLEUKIN-6 BY ALVEOLAR MACROPHAGES FROM PATIENTS WITH SARCOIDOSIS

Background: Alveolar macrophages from patients with sarcoidosis were a nalyzed for their ability to secrete tumor necrosis factor-alpha (TNF- alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). Resu lts: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrop hages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was simil ar as in healthy volunteers. In vitro stimulation of alveolar macropha ges from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-al pha, IL-1-beta, and IL-6. In a similar manner, with corresponding cell s from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or p okeweed mitogen. Conclusions: The data presented indicate that an incr eased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play critical part in the pathogenesis of sarcoidosis .