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
Zl. Lummus et al., 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, Journal of allergy and clinical immunology, 102(2), 1998, pp. 265-274
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.