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

J Allergy Clin Immunol. 1998 Aug;102(2):265-74. doi: 10.1016/s0091-6749(98)70095-8.


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.

Conclusion: 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.

MeSH terms

  • Adult
  • Antigens / immunology*
  • Asthma / blood
  • Asthma / chemically induced
  • Asthma / immunology*
  • Biomarkers, Tumor*
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Cyanates / immunology
  • Female
  • Humans
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Isocyanates / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphokines / biosynthesis
  • Male
  • Middle Aged
  • Occupational Diseases / blood
  • Occupational Diseases / chemically induced
  • Occupational Diseases / immunology*
  • Toluene 2,4-Diisocyanate / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Protein, Translationally-Controlled 1


  • Antigens
  • Biomarkers, Tumor
  • Chemokine CCL2
  • Chemokines
  • Cyanates
  • Interleukin-8
  • Isocyanates
  • Lymphokines
  • Tumor Necrosis Factor-alpha
  • Tumor Protein, Translationally-Controlled 1
  • 1,6-hexamethylene diisocyanate
  • Toluene 2,4-Diisocyanate
  • 4,4'-diphenylmethane diisocyanate