• Z L Lummus, R Alam, J A Bernstein, and D I Bernstein.
• Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio 45267-0563, USA.
• J. Allergy Clin. Immunol. 1998 Aug 1; 102 (2): 265-74.

BackgroundPrevious studies have shown a significant association between confirmed diisocyanate-induced asthma (DOA) and in vitro production of diisocyanate antigen-stimulated histamine-releasing factors by PBMCs. Chemokines found in PBMC supernatants are known to express histamine-releasing factor activity.ObjectivePBMCs of diisocyanate-exposed workers were tested in vitro for diisocyanate antigen-specific enhancement of monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3 (MCP-3), macrophage inflammatory protein-1alpha, RANTES, IL-8, and T-cell cytokines that could play a regulatory role in chemokine synthesis (IL-4, IL-5, IFN-gamma, and TNF-alpha.MethodsSecretion of chemokines and cytokines was determined by quantitative immunochemical assays of PBMC supernatants. Synthesis of mRNA for beta-chemokines was determined by reverse transcription-polymerase chain reaction.ResultsPBMCs of workers with DOA showed significantly enhanced 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.ConclusionAntigen stimulation of MCP-1 and TNF-alpha suggest that diisocyanate-specific cellular immune reactions result in activation of macrophages, which may be important in the pathogenesis of DOA.

41 keywords...

hide…