Chest
Release of Tumor Necrosis Factor-α From Human Alveolar Macrophages is Decreased in Smokers
Section snippets
Study Population
The normal population consisted of 26 healthy subjects; 13 were nonsmokers and 13 were smokers. None had a history of lung disease, and none showed evidence of lung disease by physical examination, chest radiograph, and pulmonary function tests. Their detailed demographic data and BAL findings are shown in Table 1.
The diagnosis of pulmonary sarcoidosis was established in 29 untreated patients; 13 were nonsmokers and 16 were smokers. They had a compatible clinical picture without evidence of
RESULTS
We first examined the time course of TNF-$aL release by AMs at the LPS concentration of 20 µg/ml in four patients with pulmonary sarcoidosis (two nonsmokers, two smokers). The AMs were cultured for 12, 24, 48, and 72 h, and TNF-$aL concentrations in the culture supernatants were determined by ELISA. As shown in Figure 1, the release of TNF-$aL increased over time, and plateau levels were reached by 24 h. The levels then remained stable during the following 24 h. Accordingly, a 48-h time point
DISCUSSION
We made two important observations in this study. We first confirmed previous observations that AMs from sarcoid patients have an increased capacity to release TNF-$aL. Tumor necrosis factor was first described in 1975 as a necrosing factor for solid tumors found in the sera of BCG-immunized mice challenged with LPS.16 Subsequent investigations have shown that the biologic activities of this cytokine extend well beyond the realm of antitumor biology. In the respiratory system, TNF is an
REFERENCES (35)
- et al.
Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis
Chest
(1989) - et al.
Alterations in immunoregulatory T-cell subsets in cigarette smokers: a phenotypic analysis of bronchoalveolar and blood lymphocytes
Chest
(1986) - et al.
Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells
J Biol Chem
(1991) Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis
Am Rev Respir Dis
(1984)- et al.
Interleukins in pulmonary sarcoidosis: dissociative correlation of lung interleukins 1 and 2 with the intensity of alveolitis
Am Rev Respir Dis
(1988) - et al.
Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis
J Clin Invest
(1985) - et al.
Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung
Am J Respir Cell Mol Biol
(1990) - et al.
Tumor necrosis factor production by human sarcoid alveolar macrophages
Am J Pathol
(1986) - et al.
Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis
J Lab Clin Med
(1990) Extrinsic allergic alveolitis: a disease commoner in non-smokers
Thorax
(1977)
Sarcoidosis: a disease commoner in non-smokers?
Thorax
Chest symptoms and farmer's lung: a community survey
Br J Ind Med
Lymphocyte studies in asymptomatic cigarette smokers: a comparison between lung and peripheral blood
Am Rev Respir Dis
Interleukin 1 production by alveolar macrophages is decreased in smokers
Am Rev Respir Dis
Cigarette smoking decreases interleukin 1 release by human alveolar macrophages
Am J Physiol
Proposal of standardized methods and reference for assaying recombinant human tumor necrosis factor
Jpn J Med Sci Biol
An endotoxin-induced serum factor that causes necrosis of tumors
Proc Natl Acad Sci USA
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2011, Academic RadiologyCitation Excerpt :Pathophysiologically, it has been suggested that smoking may decrease inflammatory cytokines that contribute to formation of granulomas (15). Tobacco smoke decreases the release of TNF-alpha by alveolar macrophages in normal subjects and in those with sarcoidosis (16). Similarly, nicotine has been shown to inhibit the formation of granulomas in hypersensitivity pneumonitis in a murine model (17).
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This study was supported in part by the Smoking Research Foundation of Japan and by Grants-in-Aid (02404040 and 04454248) for Scientific Research from the Ministry of Education, Science, and Culture of Japan.
Manuscript received February 24; revision accepted July 2.