Cytokine mRNA expression in isocyanate-induced hypersensitivity pneumonitis.
BACKGROUND
Diisocyanate is widely used as a polymerizing agent for manufacturing many products. However, repeated inhalation exposure to diisocyanates in the workplace can cause bronchial asthma, hypersensitivity pneumonitis (HP), and neoplasia.


OBJECTIVE
In the current study, immunological tests were conducted to explore the mechanisms involved in the pathogenesis of diisocyanate-induced HP.


METHODS
Evaluations included 4 patients with diisocyanate-induced HP, 4 volunteers with current occupational exposure to diisocyanates and 4 normal volunteers without a history of exposure to diisocyanates. IgG and IgA antibody levels to diisocyanates were determined by ELISA in sera and BAL fluids. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or in the absence of 10 microg/ml MDI-HSA (4, 4' diphenylmethane diisocyanate)-HSA (human serum albumin). (3)H-thymidine uptake, mRNA expression by RT-PCR (beta-actin, IL-1beta, IL-2R, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta) were estimated.


RESULTS
Patients with diisocyanate-induced HP had detectable IgG and IgA antibodies to diisocyanates. In addition, PBMCs from HP patients proliferated in the presence of diisocyanates and showed enhanced expression of mRNA of proinflammatory cytokines. In contrast, normal volunteers with current occupational exposure showed elevated levels of mRNA expression of IL-10 and IL-2R, suggesting the presence of sensitized cells and protection from pathology as a result of enhanced IL-10 production.


CONCLUSIONS
Patients with diisocyanate-induced HP are likely to override the protective effects of IL-10 as they express lower levels of this cytokine.
Sumi
Yuki
Y
The Pulmonary Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Kyi
Min
M
Miyazaki
Yasunari
Y
Ohtani
Yoshio
Y
Miyake
Shuji
S
Yoshizawa
Yasuyuki
Y
D000542:Alveolitis, Extrinsic Allergic / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D017953:Isocyanates / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear; D008297:Male; D009784:Occupational Diseases / Q000276:immunology; D016273:Occupational Exposure; D012333:RNA, Messenger / Q000378:metabolism*
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017953:Isocyanates; D012333:RNA, Messenger; D016753:Interleukin-10