Abstract:
:Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung, the source of provoking antigen has been found to be actinomycetes such as Micropolyspora faeni. In this study, we show that M. faeni, or antigens thereof, stimulate strong release of proinflammatory cytokines from blood monocytes and alveolar macrophages obtained from nonfarmer volunteers and naive mouse peritoneal macrophages. Interleukin-1 (IL-1) was produced by human alveolar macrophages and murine peritoneal macrophages in response to whole M. faeni and antigens thereof. IL-1 activity was detected in the supernatants at 12 h of incubation and was maximal by 24 to 36 h (200 to 400 U/ml of IL-1). A rabbit antiserum to IL-1 alpha and IL-1 beta neutralized the thymocyte-stimulating activity of the supernatants. Moreover, M. faeni (1 to 100 micrograms of antigen) elicited a strong secretion of tumor necrosis factor-alpha (TNF-alpha) from human alveolar macrophages and monocytes as well as mouse peritoneal macrophages, where 1 micrograms of M. faeni elicited the secretion of approximately 100 U of TNF-alpha from 2 x 10(5) macrophages, and 100 micrograms stimulated the release of approximately 1,000 U of bioactive TNF-alpha. One particle of whole M. faeni per cell was sufficient to induce copious release of TNF-alpha from macrophages or monocytes (100 U of bioactive TNF-alpha; 1,000 pg/ml of antigenic TNF-alpha as seen by radioimmunoassay). Both IL-1 and TNF-alpha productions stimulated by M. faeni were not abrogated by inclusion of polymyxin B. We propose that the direct stimulation of cytokines by M. faeni or antigens thereof may play an important role in HP.
journal_name
Am J Respir Cell Mol Biolauthors
Denis M,Cormier Y,Tardif J,Ghadirian E,Laviolette Mdoi
10.1165/ajrcmb/5.2.198subject
Has Abstractpub_date
1991-08-01 00:00:00pages
198-203issue
2eissn
1044-1549issn
1535-4989journal_volume
5pub_type
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