Background: Farmers may be often exposed to β-D-glucan in moldy hay, since straw for feed can be stored throughout the year. Objectives: The aim of the present study was to clarify whether levels of β-D-glucan, which modifies immune responses, are high in the respiratory tract in farmer’s lung and whether β-D-glucan participates in the pathogenesis of this condition. Methods: We measured β-D-glucan levels in the bronchoalveolar lavage fluid (BALF) of 10 patients with farmer’s lung, 4 with summer-type hypersensitivity pneumonitis (HP) and 10 healthy volunteers. Interleukin (IL)-8 and tumor necrosis factor (TNF)-α levels in BALF were measured by enzyme-linked immunosorbent assay (ELISA). We investigated the effects of β-D-glucan on nuclear factor (NF)-ĸB activation and on the release of IL-8 and TNF-α from small airway epithelial cells (SAECs) in vitro. Results: β-D-Glucan levels in the BALF of farmer’s lung patients were increased compared to those in patients with summer-type HP and in healthy volunteers. Additionally, IL-8 levels in BALF were higher in farmer’s lung than in summer-type HP, and TNF-α levels were equal in the two patient groups but raised compared to those in healthy volunteers. High, but not low, concentrations of β-D-glucan were found to induce NF-ĸB activation in SAECs. IL-8 levels in the supernatant obtained from SAEC cultures were increased following the addition of β-D-glucan in vitro. Conclusion: BALF from farmer’s lung patients showed high β-D-glucan levels, which may enhance the expression and release of cytokines through NF-ĸB activation in respiratory epithelial cells.

1.
Fink JN: Hypersensitivity pneumonitis. Clin Chest Med 1992;13:303–309.
2.
Sharma OP, Fujiwara N: Hypersensitivity pneumonitis: A noninfectious granulomatosis. Semin Respir Infect 1992;10:96–106.
3.
Salvaggio JE: Inhaled particles and respiratory disease. J Allergy Clin Immunol 1994;94:304–309.
4.
Ando M, Suga M: Hypersensitivity pneumonitis. Curr Opin Pulm Med 1997;3:391–395.
5.
Vetvicka V, Yvin JC: Effects of marine β-1,3 glucan on immune reactions. Int J Immunopharmacol 2004;4:721–730.
6.
Kawayama T, Fujiki R, Honda J, Rikimaru T, Aizawa H: High concentration of (1→3)-β-D glucan in BAL fluid in patients with acute eosinophilic pneumonia. Chest 2003;123:1302–1307.
7.
Lebron F, Vassallo R, Puri V, Limper AH: Pneumocystis carinii cell wall β-glucans initiate macrophage inflammatory responses through NF-κB activation. J Biol Chem 2003;278:25001–25008.
8.
Hahn PY, Evans SE, Kottom TJ, Standing JE, Pagano RE, Limper AH: Pneumocystis carinii cell wall β-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. J Biol Chem 2003;278:2043–2050.
9.
Schuyler M, Gott K, French V: The role of MIP-1α in experimental hypersensitivity pneumonitis. Lung 2004;182:135–149.
10.
Gudmundsson G, Hunninghake GW: Interferon-γ is necessary for the expression of hypersensitivity pneumonitis. J Clin Invest 1997;99:2386–2390.
11.
Nance S, Cross R, Fitzpatrick E: Chemokine production during hypersensitivity pneumonitis. Eur J Immunol 2004;34:677–685.
12.
Dakhama A, Israel-Assayag E, Cormier Y: Role of interleukin-2 in the development and persistence of lymphocytic alveolitis in farmer’s lung. Eur Respir J 1998;11:1281–1286.
13.
Dai H, Guzman J, Bauer PC, Costabel U: Elevated levels of soluble TNF receptors in bronchoalveolar lavage fluid in extrinsic allergic alveolitis. Clin Exp Immunol 1999;29:1209–1213.
14.
Denis M: Proinflammatory cytokines in hypersensitivity pneumonitis. Am J Respir Crit Care Med 1995;151:164–169.
15.
Barnes PJ, Karin M: Nuclear factor-κB: A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997;336:1066–1071.
16.
Blackwell TS, Christman JW: The role of nuclear factor-κB in cytokine gene regulation. Am J Respir Cell Mol Biol 1997;17:3–9.
17.
Ghosh S, Karin M: Missing pieces in the NF-κB puzzle. Cell 2002;109:81–96.
18.
Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M: Immunosuppression by glucocorticoids: Inhibition of NF-κB activity through induction of IκB synthesis. Science 1995;270:286–290.
19.
Ando M, Arima K, Yoneda R, Tamura M: Japanese summer-type hypersensitivity pneumonitis. Am Rev Respir Dis 1991;144:765–769.
20.
Monkare S: Clinical aspects of farmer’s lung: airway reactivity, treatment and prognosis. Eur J Respir Dis Suppl 1984;137:1–68.
21.
Amishima M, Munakata M, Ohtsuka Y, Satoh A, Takahashi T, Taguchi H, Nasuhara Y, Ohe M, Doi I, Homma Y: Dairy farmers have increased methacholine bronchial responsiveness independent of sensitization to mold antigens. Am J Respir Crit Care Med 1995;151:1794–1798.
22.
Obayashi T, Yoshida M, Mori T, Goto H, Yasuoka A, Iwasaki H, Teshima H, Kohno S, Horiuchi A, Ito A: Plasma (1→3)-β-D-glucan determination in the diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet 1995;345:17–20.
23.
Fogelmark B, Sjöstrand M, Rylander R: Pulmonary inflammation induced by repeated inhalations of β(1,3)-D-glucan and endotoxin. Int J Exp Pathol 1994;75:85–90.
24.
Evans SE, Hahn PY, McCann F, Kottom TJ, Pavlovic’ ZV, Limper AH: Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-κB-dependent mechanisms. Am J Respir Cell Mol Biol 2005;32:490–497.
25.
Flory CM, Jones ML, Miller BF, Warren JS: Regulatory roles of tumor necrosis factor-α and interleukin-1β in monocyte chemoattractant protein-1-mediated pulmonary granuloma formation in the rat. Am J Pathol 1995;146:450–462.
26.
Denis M, Cormier Y, Fournier M, Tardif J, Laviolette M: Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model. Am J Respir Cell Mol Biol 1991;5:477–483.
27.
Sakurai T, Ohno N, Yadomae T: Effects of fungal β-glucan and interferon-γ on the secretory functions of murine alveolar macrophages. J Leukoc Biol 1996;60:118–124.
28.
Sakurai T, Kaise T, Yadomae T, Matsubara C: Different role of serum components and cytokines on alveolar macrophage activation by soluble fungal (1→3)-β-D-glucan. Eur J Pharmacol 1997;334:255–263.
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