Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)‐8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM‐CSF and G‐CSF in the lungs of patients with ARDS and determine their relationship relative to IL‐8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme‐linked immunosorbent assay. GM‐CSF, G‐CSF and IL‐8 were all increased in the patients compared to healthy controls but concentrations of GM‐CSF were much lower than those of G‐CSF and IL‐8 (GM‐CSF

SUMMARYExtrinsic allergic alveolitis (EAA) (synonym: hypcrsensilivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocylic infiltrates in the pulmonary interstitial tissues. We have previously reported thai the numbers of lymphocytes in bronchoalveoiar iavage (BAL) samples in this disease correlate wilh leveis ofcholesierol and neutral lipid-ladcn 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which areknovtn lobe essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesteroi is capable of enhancing the antigenpresenting function of mononuciear phagocytes by moduiating the expression of HLA-D region products. Ineubation of purified monocytes from heaithy volunteers with cholesterol in serum-free medium induced a significant increase in bolh ihe percentages of monocyles expressing HLA-DQ (P< 002) and in Ihe intensity of expression of the three HLA-D sub-region products, HLA-DQ,-DP and -DR {P<0Q2. <001, <005, respeetiveiy). The choieslerol pre-incubated monocytes also exhibited enhanced antigen-presenting function (/'<005), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augmeni aniigen presentation by modulating the expression of HLA-D region products on anligen-preseniing cells. Apart from EAA. this observation may also have relevance lo inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.

Normal lung lining fluid suppresses lymphoproliferative responses. This effect is mediated by the major phospholipid components, but minor lipid components can stimulate lymphocyte proliferation. The aim of this study was to discover whether the changes in lung lipid composition reported in patients with extrinsic allergic alveolitis (EAA) might influence the levels of lymphocytes which occur in the lungs of these patients. Since cigarette smokers are less susceptible to EAA, we also investigated the effect of smoking on the lipid composition of lung lining fluid. Lung lining fluid was sampled by bronchoalveolar lavage (BAL) from 15 patients with EAA, and 9 non-smokers and 13 smokers without lung disease. The smoking controls had increases in phosphatidylethanolamine, sphingomyelin and phosphatidylglycerol, but lower levels of cholesterol and cholesterol:total phospholipid ratios compared with the nonsmoking controls. By contrast, the patients with EAA had increases in total phospholipid and sphingomyelin; there were no smoking related decreases in cholesterol; and several patients had levels of cholesterol and cholesterol:total phospholipid ratios above the upper limit for the controls. In the BAL fluids of the EAA patients, the levels.ml-1 of the immunostimulatory lipids sphingomyelin, phosphatidylethanolamine, cholesterol and cholesterol esters correlated with the number.ml-1 of lymphocytes, mast cells, neutrophils and "foamy" macrophages. Cholesterol levels (rs = 0.82) and lymphocyte counts (rs = 0.90) correlated most closely with "foamy" macrophages (p less than 0.001), suggesting that uptake of cholesterol by macrophages may enhance antigen-presenting function. These observations provide some support for the hypothesis that inflammatory reactions in the lungs might be influenced by the local lipid environment.

The aim of this study was to explore whether amounts of angiotensin converting enzyme (ACE) and lysozyme produced within the lungs correlate more closely than serum levels of these enzymes, or other inflammatory markers, with chest radiographic profusion scores, lung function and therapy response in patients with pulmonary sarcoidosis. We have studied 25 patients, and levels in bronchoalveolar lavage (BAL) were used to determine "local" enzyme production by reference to serum and lavage albumin. Before treatment, serum lysozyme levels were elevated in more patients (80%) than serum ACE levels (40%). They also gave the best overall correlation with clinical measurements prior to treatment and falls in serum lysozyme closely parallelled improvement in lung function (transfer factor for carbon monoxide (DLCO)) on therapy. The only other markers showing significant correlations with disease severity were lavage neutrophil counts per ml and "local" ACE measurements prior to treatment. The value of pre-treatment levels of the different inflammatory markers in predicting response to corticosteroid therapy was explored and the only significant finding was that BAL lymphocyte percentages and numbers.ml-1 were initially higher in patients with lower post-treatment chest X-ray scores (p less than 0.01 and p less than 0.05, respectively). We conclude that serum lysozyme levels appear to be a more useful marker of overall disease activity in sarcoidosis than measurements of other inflammatory markers. However, BAL lymphocyte counts were the best predictive marker of radiographic response to corticosteroids.

Summary Previous reports suggest that blood monocytes and tissue epithelioid cells in patients with sarcoidosis are‘activated’, but few studies have been undertaken on human alveolar macrophages. In the present study, bronchoulveolar lavage samples have been obtained from eighteen patients with sarcoidosis and these have been compared with twenty controls and twenty‐nine patients with non‐granulomatous chronic inflammatory interstitial lung disease (cryptogenic fibrosing alveolitis). Assessment of the functional state of the macrophages was made by measurements of C3b receptor sites on the cell membrane, intra and extracellular lysosomal enzyme (β‐D‐glucosaminidase) and the degree of spreading of macrophages on glass. C3b receptor sites and intracellular levels of lysosomal enzyme were significantly reduced in sarcoidosis compared to controls; levels of extracellular enzyme in the lavage supernatant fluid and macrophage spreading were similar to controls. These features suggest that alveolar macrophages from patients with sarcoidosis are not “activated”. By contrast, in cryptogenic fibrosing alveolitis. macrophages show a greater extracellular intracellular ratio of lysosomal enzyme and more spreading, suggestive of ‘activation’.