Against our expectation, in NC the levels of BALF cell 2,5AS activity were prominently high as compared with the levels of PBML 2,5AS activity (approximately sevenfold of the PBML activity). To clarify whether the levels of 2,5AS activity depend on cell differentiation, we analyzed the correlations of the 2,5AS activity levels to ratios of cells composed in PBML and BALF cells, and the levels of 2,5AS activity of cells isolated from PBML and BALF in patients with SAR and IPF and NC. The levels of 2,5AS activity of PAM are not increased as compared with those of lung lymphocytes in patients with SAR and IPF as well as NC. There were no significant differences among the levels of 2,5AS activity in cells isolated from PBML (whole cells, lymphocytes, and monocytes). Witt et al also reported that there are no significant differences between the activity of monocytes and lymphocytes in peripheral blood. The increased levels of the BALF cell 2,5AS activity appear to be independent of cell differentiation in BALF cells. The levels of BALF cell 2,5AS activity seem not to be influenced by smoking. The elevated levels of BALF cell 2,5AS activity in NC indicate high levels of IFN production in the alveolar space. This is conceivable since lung is the organ that defends itself from viral and bacterial infection and foreign particles. canadian health&care mall
Regarding IFN production in the circulation of patients with SAR, there have been some reports, and they showed different results; some showed the elevation of IFN production in the circulation of patients with SAR, while others showed that a trace level of IFN was detected in sera of patients with SAR. We think that these results may be influenced by the sensitivity of the assay to detect a serum IFN level. Regarding IFN production in BALF, there have been no reports (to our knowledge) of measuring directly IFN levels in BALF, although increase of spontaneous release of IFN-gamma from BALF cells during cultivation has been reported. The 2,5AS activity, although it is indirect evidence of IFN production and there is no information of IFN producing cells, seems to reflect in vivo IFN production in the circulation and the alveolar space. The present results clearly demonstrated that the levels of PBML and BALF cell 2,5AS activity in patients with SAR were prominently high suggesting that IFN levels are markedly increased both in the circulation and the alveolar space of patients with SAR.
We also showed that the levels of PBML 2,5AS activity were prominently high in patients with IPF, although the levels of BALF cell 2,5AS activity were not enhanced. This result suggests high levels of circulating IFN in patients with IPF, and in vivo IFN production of IPF may be promoted into the circulation rather than into the alveolar space. Robinson and Rose reported spontaneous release of IFN-gamma was increased in BALF cells of a number of patients with pulmonary fibrosis. Inter-feron-gamma in vitro spontaneous release from BALF cells was increased in 44 percent (8 of 18 cases) of patients with pulmonary fibrosis associated with collagen diseases and in 18 percent (4 of 22 cases) in patients with IPF. Low levels of BALF cell 2,5AS activity in patients with IPF suggest that IFN levels may not be so high in the alveolar space and/ or BALF may not reflect the alveolar conditions of IPF exactly, since recovery rates of BALF in IPF patients are low due to histologic changes such as interstitial fibrosis, collapse of alveolar architectures, and honeycombing.
Although it remains to be unclear that IFN plays a pivotal role in the mechanisms of fibrosis and granuloma formation in the lung, it should be emphasized that IFN production, which is distinct evaluation from in vitro spontaneous release, is greatly enhanced in the circulation and the lung of patients with SAR and in the circulation of patients with IPF. Whether in vivo IFN production in the circulation and/or in the alveolar space may contribute to the onset and disease progression of SAR and IPF must be further elucidated. Further studies are needed to clarify the discrepancy of IFN production between the circulation and the alveolar space of IPF.