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A possible role for hepatitis C virus (HCV) infection in the pathogenesis of idiopathic pulmonary fibrosis (IPF) has recently been suggested on the basis of an unusually high seroprevalence rate of anti-HCV in such patients from Japan. In an attempt to confirm these findings, we tested sera from 62 patients with IPF by two second-generation anti-HCV ELISAs. Only one serum was reactive. Serum from this patient gave an indeterminate result when tested by four-antigen RIBA (c22 band only), and it was negative for the presence of HCV RNA when tested by the reverse transcriptase polymerase chain reaction assay. HCV infection is thus no more prevalent in patients with IPF from the UK than in the general population.

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay (ELISA) in 66 patients (46 male and 20 female; mean age +/- SEM, 61.5 +/- 10.1 yr) with idiopathic pulmonary fibrosis (IPF). Nineteen (28.8%) were positive for this test. The frequency of HCV positiveness was significantly higher in the patients with IPF than in the 9,464 control subjects, whose ages were comparable with those of the patients (3.66%, p less than 0.05). Importantly, 12 of the 19 patients with IPF and positive ELISA results (63.2%) had positive results on the Chiron recombinant immunoblotting assay (RIBA), which is known to be more specific for HCV. We judged the 12 perceptible reactions as eight reactive and four indeterminate. When we examined liver function retrospectively, only two of eight patients who tested positive for the HCV had liver dysfunction, suggesting that anti-HCV positivity in IPF was not observed as a result of liver disease. These results lead us to speculate that HCV infection may play an important role in the pathogenesis of IPF, or that the sera of patients with IPF may contain some antibody against an unknown epitope and cross-react with the anti-HCV assay.

The involvement of Epstein-Barr virus (EBV) in the pathogenesis of lymphocytic interstitial pneumonia (LIP) was investigated using an in situ hybridization technique. Archival lung tissue samples from 14 patients (six men and eight women with a mean age of 58 +/- 3 yr) in whom a diagnosis of LIP had been previously established were retrospectively examined and compared with samples from 10 patients (six men and four women with a mean age of 58 +/- 3 yr) with idiopathic pulmonary fibrosis (IPF) who served as control subjects. In patients with LIP, the immunophenotype of the lymphocytic infiltrate was determined by using monoclonal antibodies to both pan-B-cell and pan-T-cell markers. In situ hybridization studies were performed by using the BamHI-W region of the EBV genome as a probe and a colorimetric detection method. The immunophenotyping studies showed that the interstitial infiltrate in LIP was primarily made up of B-lymphocytes, particularly within the lymphoid aggregates, whereas T-lymphocytes were sparsely distributed along the alveolar septa. The in situ hybridization studies showed the presence of cells bearing the EBV genome in nine cases of LIP and in two cases of IPF (p less than 0.05, Fisher's exact test). In LIP, the EBV-positive cells were observed in both enlarged and normal septa and occasionally within the lymphoid aggregates. We conclude that EBV may promote the proliferation of B-lymphocytes in a substantial number of patients with LIP.

Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial pneumonia with infiltration of mononuclear cells in the interstitium, the pathogenesis of which is unknown. We studied six patients with LIP to investigate the immunologic characteristics of lymphocytes in the lower respiratory tract and the possible involvement of human T-cell lymphotropic virus type I (HTLV-I), which is endemic in the southwestern region of Japan. Lymphocyte surface antigen phenotyping in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) cells revealed a predominance of CD8 positive (suppressor/cytotoxic) T-lymphocytes (PB: 51.5 +/- 0.8%; BALF: 52.9 +/- 12.7%), which consisted of an increased number of CD8 positive CD11 negative (cytotoxic) T-lymphocytes (PB: 30.2 +/- 10.5%; BALF: 57.1 +/- 11.8%). The increased number of cytotoxic T-lymphocytes among patients with LIP led us to investigate the possible involvement of HTLV-I, EB virus, and HIV in patients with chronic interstitial disorders of LIP, sarcoidosis, and IPF. The seropositivity rate for HTLV-I was 83.7% (5/6) in patients with LIP, 3.1% (1/28) with IPF, 7.1% (2/28) with sarcoidosis, and 0% (0/28) in healthy volunteers. None of the patients were seropositive for either HIV or EB virus. These results suggest that HTLV-I may be involved in a direct or indirect role in the pathologic mechanisms through the host immune reaction to the antigenicity of the virus and/or the possible involvement of viral regulatory genes to disrupt the normal immune reaction of the host.

Three patients had a typical clinical, functional, and histologic pattern of lymphoid interstitial pneumonitis (LIP). All 3 also had a marked follicular and interfollicular hyperplasia of peripheral lymph nodes. A benign lymphocytic infiltration was seen in the kidneys in 2 patients, in the liver of 1 of these, and in the nasopharynx and the bone marrow in another. This LIP, associated with other diffuse benign lymphocytic infiltrates, could be part of AIDS-related manifestations. The patients originated from central Africa (2 patients) and Haiti (1 patient) where AIDS is endemic. They had several immune abnormalities frequently observed in AIDS such as a polyclonal hyperimmunoglobulinemia and, in the 2 patients studied, a decreased number of T4 lymphocytes and an inverted T4/T8 blood lymphocyte ratio. All 3 patients had serum antibodies to human T-cell leukemia viruses.

The accumulation of inflammatory and immune effector cells in the lungs of patients at early stages of interstitial lung disease has been well documented, but little is known about the functional activity of these cells, particularly alveolar macrophages. The purpose of the experiments described here was to determine whether alveolar macrophages from patients with idiopathic pulmonary fibrosis (IPF) differed from alveolar macrophages of normal subjects using a model system that assesses a component of cell-mediated immunity. Alveolar macrophages were tested for their ability to phagocytose and kill the facultative intracellular bacterium Listeria monocytogenes. Because this system requires the stimulation of macrophages by antigen-specific T-cells, it allows the assessment of effector functions of macrophages found in the lower respiratory tract of patients with IPF. Data showed that alveolar macrophages from normal subjects both phagocytosed and killed those bacteria. However, alveolar macrophages from patients with IPF phagocytosed bacteria normally but expressed little bactericidal or bacteriostatic activity. Further, we found no difference in HLA-DR expression by normal and IPF alveolar macrophages. Therefore, it does not appear that this defect in bactericidal activity in IPF macrophages results from a defect in the antigen-presenting function of these cells. These data suggest that alveolar macrophages from patients with IPF express a functional deficiency in their ability to kill facultative intracellular bacteria.