Diisocyanate antigen–enhanced production of monocyte chemoattractant protein-1, IL-8, and tumor necrosis factor-α by peripheral mononuclear cells of workers with occupational asthma,☆☆,

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Abstract

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-1α, RANTES, IL-8, and T-cell cytokines that could play a regulatory role in chemokine synthesis (IL-4, IL-5, IFN-γ, and TNF-α). Methods: Secretion of chemokines and cytokines was determined by quantitative immunochemical assays of PBMC supernatants. Synthesis of mRNA for β-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-α. IFN-γ, IL-4, and IL-5 were not enhanced in subjects with DOA. Conclusion: Antigen stimulation of MCP-1 and TNF-α suggest that diisocyanate-specific cellular immune reactions result in activation of macrophages, which may be important in the pathogenesis of DOA. (J Allergy Clin Immunol 1998;102:265-74.)

Section snippets

Reagents

RPMI 1640, HBSS, glutamine, penicillin-streptomycin, and HEPES were obtained from GIBCO Laboratories (Grand Island, NY); FBS was obtained from HyClone Laboratories, Inc (Logan, Utah); BSA (Fraction V, crystalline), alkaline phosphatase-goat anti-human IgG, alkaline phosphatase mouse monoclonal anti-rabbit IgG, and sodium pyruvate were obtained from Sigma Chemicals Co (St. Louis, Mo); goat anti-human IgE and alkaline phosphatase-rabbit anti-goat IgG were obtained from Kierkegard & Perry

Antigen enhancement of HRF and chemokine synthesis

Clinical characteristics of workers with DOA and antibody and cytokine responses are shown in Tables I and II.

. Description of diisocyanate-exposed workers and control subjects

Empty CellEmpty CellExposureEmpty CellEmpty CellEmpty CellEmpty CellEmpty CellEmpty CellEmpty Cell
Worker nos.ChemicalDuration (mos)*(mos)Cessation diagnosisClinical challengeBronchial AB‡MCP-1§IL-8§TNF- α §
Group 1:
Symptomatic
workers
1MDI, TDI4819OA+(lab)∥, LAR¶IgG++
2MDI2510OA+(work)#+++
3HDI, MDI10032OA+(work)+++
4HDI601OA+(work)IgE, IgG++
5HDI24019OA+(work)++
6HDI1211OA+(work)IgE, IgG+++
7HDI, MDI6020OA+(work)

DISCUSSION

In this study workers with confirmed DOA exhibited enhanced in vitro diisocyanate-HSA antigen-stimulated synthesis of MCP-1, IL-8, and TNF-α. Diisocyanate-antigen enhancement of MCP-1 and IL-8 was demonstrated in 7 of 8 workers with confirmed OA. Of these subjects, 6 had been completely restricted from exposure to diisocyanate chemicals for longer than 10 months, indicating persistence of diisocyanate-responsive mononuclear cells. Diisocyanate-antigen specificity of MCP-1 production was

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    From athe Department of Internal Medicine, Immunology Division, University of Cincinnati College of Medicine, Cincinnati; and bthe Department of Internal Medicine, Allergy Division, University of Texas Medical Branch, Galveston.

    ☆☆

    Reprint requests: Zana L. Lummus, University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology, 231 Bethesda Avenue, Cincinnati, OH 45267-0563.

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