Am. J. Respir. Crit. Care Med., Volume 163, Number 2, February 2001, 379-382

Tumor Necrosis Factor- 308 Promoter Gene Polymorphism and Increased Tumor Necrosis Factor Serum Bioactivity in Farmer's Lung Patients

BERNHARD M. SCHAAF, ULRIKE SEITZER, VERA PRAVICA, SVEN P. ARIES, and PETER ZABEL

Medical Clinic II, University of Lübeck, Lübeck, Germany; Department of Immunology and Cell Biology, and Medical Clinic, Research Center Borstel, Borstel, Germany; and School of Biological Sciences, University of Manchester, Manchester, United Kingdom

Hypersensitivity pneumonitis (HP) represents an immunologic reaction of the pulmonary parenchyma to an inhaled agent. Since tumor necrosis factor (TNF)- is thought to be involved in the pathogenesis of HP, and polymorphisms in the TNF genes have been associated with variations in the production of TNF-, we investigated the serum bioactivity and genotype of TNF in HP. TNF bioactivity was measured after hay dust challenge in eight patients with farmer's lung (Group A) and in 12 healthy, sensitized (antibody-positive) controls (Group B). Genotyping for the 308 TNF- promoter polymorphism and the TNF- intron 1 gene polymorphism was performed in 20 patients with farmer's lung, 25 patients with pigeon breeder's lung, and 216 controls. TNF bioactivity increased in Group A at 4 to 10 h after hay dust challenge, but not in Group B (p < 0.05). The frequency for the TNFA2 allele, a genotype associated with high TNF- production in vitro, was significantly higher in farmer's lung patients (frequency [f] = 0.43, p = 0.0012) than in controls (f = 0.19) or patients with pigeon breeder's lung (f = 0.16). Genotyping for TNF- revealed no significant abnormalities. Thus, increased production of TNF- after hay contact, and a genetic predisposition to TNF- production, are implicated in the pathogenesis of alveolitis in farmer's lung.

This article has been cited by other articles:

				M. L. Bustos, S. Frias, S. Ramos, A. Estrada, J. L. Arreola, F. Mendoza, M. Gaxiola, M. Salcedo, A. Pardo, and M. Selman Local and Circulating Microchimerism Is Associated with Hypersensitivity Pneumonitis Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 90 - 95. [Abstract] [Full Text] [PDF]

				S. J. Hwang, S. Kim, W. S. Park, and D. H. Chung IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-{gamma}-Producing Neutrophils J. Immunol., October 15, 2006; 177(8): 5258 - 5268. [Abstract] [Full Text] [PDF]

				H Marotte, B Pallot-Prades, L Grange, J Tebib, P Gaudin, C Alexandre, J L Blond, M A Cazalis, B Mougin, and P Miossec The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population Ann Rheum Dis, March 1, 2006; 65(3): 342 - 347. [Abstract] [Full Text] [PDF]

				M.-R. Blanchet, E. Israel-Assayag, and Y. Cormier Inhibitory Effect of Nicotine on Experimental Hypersensitivity Pneumonitis In Vivo and In Vitro Am. J. Respir. Crit. Care Med., April 15, 2004; 169(8): 903 - 909. [Abstract] [Full Text] [PDF]

				S J Bourke, J E Calvert, C I Baldwin, and S Worthy Occupational extrinsic allergic alveolitis Imaging, March 1, 2003; 15(1): 23 - 30. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Tuberculosis, Lung Infections, Interstitial Lung Disease, and Socioeconomic Issues in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 631 - 641. [Full Text] [PDF]

				E. L. CORBETT, N. MOZZATO-CHAMAY, A. E. BUTTERWORTH, K. M. DE COCK, B. G. WILLIAMS, G. J. CHURCHYARD, and D. J. CONWAY Polymorphisms in the Tumor Necrosis Factor-alpha Gene Promoter May Predispose to Severe Silicosis in Black South African Miners Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 690 - 693. [Abstract] [Full Text] [PDF]

				W. Merrill Hypersensitivity Pneumonitis : Just Think of It! Chest, October 1, 2001; 120(4): 1055 - 1057. [Full Text] [PDF]

				S.J. Bourke, J.C. Dalphin, G. Boyd, C. McSharry, C.I. Baldwin, and J.E. Calvert Hypersensitivity pneumonitis: current concepts Eur. Respir. J., July 1, 2001; 18(32_suppl): 81S - 92s. [Abstract] [Full Text] [PDF]