DIISOCYANATE ANTIGEN-ENHANCED PRODUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1, IL-8, AND TUMOR-NECROSIS-FACTOR-ALPHA BY PERIPHERAL MONONUCLEAR-CELLS OF WORKERS WITH OCCUPATIONAL ASTHMA

Background: Previous studies have shown a significant association betw een confirmed diisocyanate-induced asthma (DOA) and in vitro productio n of diisocyanate antigen-stimulated histamine-releasing factors by PB MCs. Chemokines found in PBMC supernatants are known to express histam ine-releasing factor activity. Objective: PBMCs of diisocyanate-expose d workers were tested in vitro for diisocyanate antigen-specific enhan cement of monocyte chemoattractant protein-1 (MCP-1), monocyte chemoat tractant protein-3 (MCP-3), macrophage inflammatory protein-1 alpha, R ANTES, IL-8, and T-cell cytokines that could play a regulatory role in chemokine synthesis (IL-4, IL-5, IFN-gamma, and TNF-alpha). Methods: Secretion of chemokines and cytokines was determined by quantitative i mmunochemical assays of PBMC supernatants. Synthesis of mRNA for beta- chemokines was determined by reverse transcription-polymerase chain re action. Results: PBMCs of workers with DOA showed significantly enhanc ed secretion for MCP-1 compared with diisocyanate-exposed asymptomatic workers (P <.05). In vitro induction of antigen-stimulated MCP-1 mRNA synthesis in cultured PBMCs was demonstrated by reverse-transcription polymerase chain reaction. Quantitation of cytokines in supernatants showed increased mean production of IL-8 and TNF-alpha. IFN-gamma, IL- 4, and IL-5 were not enhanced in subjects with DOA. Conclusion: Antige n stimulation of MCP-1 and TNF-alpha suggest that diisocyanate-specifi c cellular immune reactions result in activation of macrophages, which may be important in the pathogenesis of DOA.