Increased levels of interleukin-6 are associated with lymphocytosis in bronchoalveolar lavage fluids of idiopathic nonspecific interstitial pneumonia.

Local overexpression of interleukin-6 (IL-6) experimentally induces lymphocytic infiltration in the bronchial tree of rat. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia/fibrosis (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid when compared with usual interstitial pneumonia (UIP). To reveal a relation of IL-6 with the lymphocyte infiltration of NSIP, IL-6 was measured in BAL fluids of idiopathic NSIP (n = 7), idiopathic UIP (n = 16), and normal control subjects (n = 45). IL-6-producing sites were assessed by IL-6 protein stain on biopsy specimens of NSIP, UIP, and normal lung of mediastinal tumors. Lymphocyte numbers and IL-6 levels in BAL fluids were higher in NSIP than those in UIP (p < 0.01, respectively), which were also higher when compared with those of normal control subjects (p < 0.01, respectively). In NSIP, the levels of IL-6 correlated with the number of lymphocytes (r = 0.93, p < 0.01). UIP cases were divided into two groups: high-UIP (n = 7) or low-UIP (n = 9) according to IL-6 levels greater than or within the 95 percentile of normal control subjects, respectively. The high-UIP group had BAL lymphocytosis when compared with the low-UIP group (p < 0.05). IL-6 stained on epithelial cells of the bronchial tree and on alveolar macrophages of NSIP and UIP. In conclusion, the lymphocytosis in BAL fluid of patients with NSIP and a subgroup of UIP is associated with the high levels of IL-6 and its sources are the epithelial cells of the small airway and the alveolar macrophages.

Interleukin (IL)-5 downregulates tumor necrosis factor (TNF)-induced eotaxin messenger RNA (mRNA) expression in eosinophils. Induction of eotaxin mRNA by TNF and IL-5 in eosinophils.

An eotaxin is a chemoattractant specific for eosinophils that are known to play a role in helminth infection and allergic responses. Although several cellular sources have been reported to produce eotaxin, it would be interesting to know whether eosinophils are able to produce their own eotaxin and participate in recruitment of themselves in response to inflammation. To this end, a cloned eotaxin complementary DNA was transcribed in vitro to use as a probe for detecting eotaxin messenger RNA (mRNA), and eotaxin protein levels were determined by enzyme-linked immunosorbent assay. Eotaxin mRNA was, as analyzed by in situ hybridization, rarely detectable in unstimulated eosinophils, but was strongly induced in eosinophils when stimulated with tumor necrosis factor (TNF). Interleukin (IL)-5, which is known to be a major factor of eosinophil survival in vivo and in vitro, was also able to induce a modest level of eotaxin mRNA but inhibited TNF-induced eotaxin mRNA expression in a dose-response manner. Dexamethasone inhibited TNF-induced eotaxin mRNA expression. This result was consistent with that from reverse transcription/polymerase chain reaction followed by Southern blot analysis. Unlike the little expression of eotaxin mRNA in the absence of stimuli, the measurement of eotaxin protein revealed that a considerable amount of eotaxin protein was constitutively produced in unstimulated eosinophils. Its expression was upregulated by TNF and IL-5 as well. However, the inhibitory effect of IL-5 on TNF-mediated eotaxin protein production was not as pronounced as that on eotaxin mRNA induction. Collectively, these data reflect the complex physiology of eosinophils in the expression of eotaxin gene upon the exposure to their survival and/or death factors.

Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways.

Interleukin (IL)-3, IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) prolong the survival of eosinophils, which are conspicuous in asthmatic airways, but it is still controversial which one plays a major role in enhancing the survival of eosinophils in asthmatic airways. The role of these cytokines in airway eosinophilia was investigated using bronchoalveolar lavage (BAL) fluids from 11 symptomatic and nine asymptomatic patients with asthma and eight normal subjects. Eosinophil survival-enhancing activity (ESEA) was measured by a numerical change in viable eosinophils isolated from the peripheral blood of atopic patients and cultured with BAL fluids. ESEA was characterized by neutralization with antibodies to IL-3, IL-5 and/or GM-CSF. The differential count of BAL cells was achieved using Diff-Quik stain. T-cell subsets and activated T-cells were analysed by flow cytometry with dual stain using monoclonal antibodies to CD3, CD4, CD8 and CD25. ESEA was detected in eight of 11 BAL fluids of symptomatic asthma, but not in those of normal controls or asymptomatic asthmatics. In six symptomatic asthmatics, the mean percentage of inhibition in ESEA by anti-GM-CSF was higher than that of anti-IL-5 as well as anti-IL-3 (p<0.05). A mixture of antibodies to IL-3, IL-5 and GM-CSF totally inhibited the ESEA in four cases. The ESEA correlated with the percentage of eosinophils (p<0.05) and that of CD25(+)CD4 lymphocytes (p<0.05) of BAL cells. In conclusion, granulocyte macrophage colony-stimulating factor, rather than interleukin-3 or -5, is associated with eosinophil survival-enhancing activity inside the airways of symptomatic asthmatics. The activation of CD4 lymphocytes is related to the elevation of such activity.

The T cell receptor subsets of lymphocytes in bronchoalveolar lavage in patients with active pulmonary tuberculosis.

STUDY OBJECTIVE: To determine whether or not the levels of gamma/delta lymphocytes increase in bronchoalveolar lavage (BAL) fluid from patients with pulmonary tuberculosis. DESIGN: Prospective data collection relating to cells in BAL fluid and peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis and control subjects. SETTING: A university hospital, from March 1990 to December 1993. PATIENTS: Thirteen patients with pulmonary tuberculosis who were diagnosed by culture of Mycobacterium tuberculosis from their sputum of BAL fluid and/or clinical response were enrolled in the study. Fifteen healthy volunteers participated as control subjects. MEASUREMENTS AND RESULTS: The differential cell counts in BAL fluid were made by Diff-Quik stain. The percentages of T-cell receptor (TCR) (gamma/delta and alpha/beta)-positive lymphocytes and interleukin 2 (IL-2) receptor-positive CD3 lymphocytes in BAL fluid and peripheral blood were measured by dual scan with flow-cytometry. The percentage and absolute number of lymphocytes and the percentages of CD3+, IL2R+ lymphocytes in BAL fluid significantly increased in patients with tuberculosis when compared with those of control subjects. The percentages and numbers of gamma/delta and alpha/beta TCR-positive lymphocytes in BAL fluid and PBMC from patients with tuberculosis and indistinguishable from those of control subjects. CONCLUSIONS: gamma/delta Lymphocytes do not appear to have as much meaning in patients as they do in animal studies.

A case of bronchiolitis obliterans organizing pneumonia associated with adenovirus.

A 58-year-old man described a short history of dyspnea and a preceding flu like illness with roentgenographic features of an interstitial lung disease. An open lung biopsy specimen from him showed bronchiolitis obliterans with organizing pneumonia (BOOP). Adenovirus was isolated from a throat swab. There was both clinical and radiographic improvement with supportive care. We herein report a first case of BOOP associated with adenovirus in Korea.