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. Objectives: 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 µg/ml MDI-HSA (4, 4′ diphenylmethane diisocyanate)-HSA (human serum albumin). 3H-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.

Vandenplas O, Malo JL, Saetta M, Mapp CE, Fabbri LM: Occupational asthma and extrinsic alveolitis due to isocyanates: Current status and perspectives. Br J Ind Med 1993;50:213–228.
Vandenplas O, Malo JL, Dugas M, Cartier A, Desjardins A, Levesque J, Shaughnessy MA, Grammer LC: Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to diphenylmethane] diisocyanate (MDI). Am Rev Res Dis 1993;147:338–346.
Raulf-Heimsoth M, Baur X: Pathomechanisms and pathophysiology of isocyanate-induced diseases – Summary of present knowledge. Am J Ind Med 1998;34:137–143.
Hunninghake GW, Gadek JE, Kawanami O, Ferrans VJ, Crystal RG: Inflammatory and immune processes in the human lung in health and disease: Evaluation by bronchoalveolar lavage. Am J Pathol 1979;97:149–206.
Karol MH, Hauth BA, Alarie Y: Pulmonary hypersensitivity to hexyl isocyanate-ovalbumin aerosol in guinea pigs. Toxicol Appl Pharmacol 1979;51:73–80.
Yoshizawa Y, Ohtsuka M, Noguchi K, Uchida Y, Suko M, Hasegawa S: Hypersensitivity pneumonitis induced by toluene diisocyanate: Sequelae of continuous exposure [see comments]. Ann Intern Med 1989;110:31–34.
Baur X: Hypersensitivity pneumonitis (extrinsic allergic alveolitis) induced by isocyanates. J Allergy Clin Immunol 1995;95:1004–1010.
Grammer LC, Harris KE, Malo JL, Cartier A, Patterson R: The use of an immunoassay index for antibodies against isocyanate human protein conjugates and application to human isocyanate disease. J Allergy Clin Immunol 1990;86:94–98.
Baur X: Immunologic cross-reactivity between different albumin-bound isocyanates. J Allergy Clin Immunol 1983;71:197–205.
Schuyler M, Gott K, Fei R, Edwards B: Experimental hypersensitivity pneumonitis: Location of transferring cells. Lung 1998;176:213–225.
Schuyler M, Gott K, Shopp G, Crooks L: CD3+ and CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis. Am Rev Respir Dis 1992Dec;146:1582–1588.
Gudmundsson G, Bosch A, Davidson BL, Berg DJ, Hunninghake GW: Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice. Am J Respir Cell Mol Biol 1998;19:812–818.
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