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 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.


OBJECTIVE
PBMCs 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.


METHODS
Secretion 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.


RESULTS
PBMCs 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.


CONCLUSIONS
Antigen 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.
Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio 45267-0563, USA.
Z L
ZL
Lummus
R
R
Alam
J A
JA
Bernstein
D I
DI
Bernstein
D000328:Adult; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D014408:Biomarkers, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003485:Cyanates / Q000276:immunology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D017953:Isocyanates / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D000090324:Tumor Protein, Translationally-Controlled 1; D001559:Benzhydryl Compounds
D000941:Antigens; D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D018925:Chemokines; D003485:Cyanates; D016209:Interleukin-8; D017953:Isocyanates; D008222:Lymphokines; D014051:Toluene 2,4-Diisocyanate; D014409:Tumor Necrosis Factor-alpha; D000090324:Tumor Protein, Translationally-Controlled 1; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds