Physiologic concentrations of homocysteine inhibit the human plasma GSH peroxidase that reduces organic hydroperoxides

The plasma reduced glutathione (GSH) selenoperoxidase is a highly conserved enzyme. Furthermore, a small clinical study reported that patients with severe atherosclerosis had low peroxidase activities. Together these observations suggest that the peroxidase is important in preventing atherosclerosis. Yet others have reported that when the assay was run in Tris buffer, it was inactive with the concentrations of GSH found in the plasma. Second, it is known that hyperhomocysteinemia increases the rate of atherogenesis. Because there is some homology between homocysteine and the cysteine in GSH, the question is whether the hyperhomocysteinemia effect may be due to inhibition of the peroxidase. We purified the peroxidase from human plasma and determined its activity by a coupled spectrophotometric assay and a substrate disappearance chemiluminescence assay. When the peroxidase activity was determined in phosphate-buffered saline solution (PBS), there was significant activity with the reported plasma GSH concentrations (5 to 20 micromol/L). The peroxidase was exclusively in the HDL fraction. There was no correlation between the peroxidase activity and the HDL or LDL cholesterol concentrations. Finally, at physiologic concentrations of GSH (9 micromol/L), the peroxidase was inhibited by physiologic, free homocysteine concentrations (1 to 5 micromol/L). These data suggest that the peroxidase is active in vivo and may be important in protecting the endothelium from atherosclerosis by preventing oxidant injury. The homocysteine inhibition of the peroxidase suggests a possible biochemical basis for the observed association between hyperhomocysteinemia and cardiovascular disease. Our studies imply that low concentrations of this peroxidase may be an independent risk factor for atherosclerosis.     

Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects.

Kininogenase activity was detected by cleavage of radiolabeled substrate (125I-high molecular weight kininogen [HMWK]) in 22 of 24 bronchoalveolar lavage (BAL) fluid samples from 17 asthmatics who either responded to aerosolized allergen challenge or had symptoms of active asthma. In contrast, six of seven normal controls lacked enzymatic activity. Levels of free immunoreactive kinin found in BAL fluid correlated with the presence of kininogenase activity (P = 0.002). The cleavage pattern of 125I-HMWK by the BAL fluid kininogenase (a dominant 65,000-mol wt fragment), and synthetic inhibitor profile (phe-phe-arg-CH2Cl and phenylmethylsulfonyl fluoride) were compatible with a tissue kallikrein. Peak kininogenase activity eluted at an apparent molecular weight of 20,000-34,000 by HPLC gel filtration. Its antigenic identity was established by immunoblotting with anti-human urinary kallikrein antibody and its activity was inhibited by this antibody. Lysylbradykinin was generated during incubation of fractionated BAL fluid and purified HMWK, the characteristic cleavage product of the tissue kallikreins. We conclude that elevated amounts of tissue kallikrein and kinin are present in the bronchoalveolar spaces of asthmatic subjects. Kinin generation may contribute to the asthmatic response directly through edema formation and smooth muscle contraction and by augmenting release and/or production of preformed (histamine) and secondary mediators such as leukotrienes and platelet-activating factor.     

PEEP decreases atelectasis and extravascular lung water but not lung tissue volume in surfactant-washout lung injury

Objective To examine the effects of positive end-expiratory pressure (PEEP) on extravascular lung water (EVLW), lung tissue, and lung volume.Design and setting Experimental animal study at a university research facility.Subjects Fifteen adult sheep.Interventions All animals were studied before and after saline washout-induced lung injury while ventilated with sequentially increasing PEEP (0, 7, 14, or 21 cmH₂O).Measurements and results Lung volume was determined by computed tomography and EVLW by the thermal dye dilution technique. Saline washout significantly increased lung tissue volume (21±3 to 37±5 ml/kg) and EVLW (9±2 to 36±9 ml/kg). While increasing levels of PEEP reduced EVLW (30±7, 24±8, and 18±4 ml/kg), lung tissue volume remained constant. Total lung volume significantly increased (50±8 ml/kg at PEEP 0 to 77±12 ml/kg at PEEP 21). Nonaerated lung volume significantly decreased and was closely correlated with the changes in EVLW (r=0.67). In addition, a highly significant correlation was found between PEEP-induced decrease in nonaerated lung volume and decrease in transpulmonary shunt (r=0.83).Conclusions The main findings are as follows: (a) PEEP effectively decreases EVLW. (b) The decrease in EVLW is closely correlated with the PEEP-induced decrease in nonaerated lung volume, making EVLW a valuable bedside parameter indicating alveolar recruitment, similar to measurements of transpulmonary shunt. (c) As excess tissue volume remained constant, however, EVLW may not be suitable to reflect overall severity of lung diseaseThis study was supported by a grant from the Faculty of Clinical Medicine, University of Mannheim.     

Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined by the American College of Chest Physicians/Society of Critical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 septic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined in serum. In some experiments, IL-18 mRNA levels were determined in peripheral blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 levels were significantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment. These data might underscore the role of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue damage. Furthermore, these findings raise the notion that mediator measurement in immunologically active organs might serve as pivotal indicators of sepsis prior to the actual fulfillment of specific clinical criteria that defines the patient as being septic.     

Detection of peripheral blood and bronchoalveolar lavage fluid lymphocytes in rat lung transplantation for early diagnosis of rejection

Left lung transplantation was performed in two combinations of rat strains. In group 1, lung grafts were rejected within 7 day postoperatively, and in group 2, grafts were rejected within 18 day postoperatively. The histological appearance of rejection was classified into 4 stages, and lymphocytes from peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were collected at each stage. In group 1, a significant decrease in the number of lymphocytes in PB was observed as the rejection progressed, whereas the number of lymphocytes in PB increased slightly in group 2. The number of total cells in BALF increased significantly as the rejection progressed in both groups. A marked increase in the value of spontaneous blastogenesis (SB) was observed in stage 2 in BALF lymphocytes, whereas that in PB lymphocytes was found to increase after stage 3 in both groups. The ratio of T-helper/T-nonhelper did not change significantly in PB lymphocytes in both groups. On the other hand, a significant decrease in the value of T-helper/T-nonhelper (less than 1.0) was observed in BALF at stage 3 and 4 in both groups. These results show that the studies of BALF lymphocytes were very useful for early diagnosis of rejection in lung transplantation.     

灌洗液红细胞计数与肺保护液量相关关系的实验研究

现代肺移植技术已成为抢救终末期不可逆性肺病患者生命的新技术,而肺移植是大器官移植中最后进行实验移植研究的,临床肺移植的进展也落后于其它器官,供肺的保护直接关系到肺移植的成败。但当前并无一个量化的指标来显示保护液的量是否充分以及肺组织内是否有血液成分残留。基于     

Omega-oxidized leukotriene B4 detected in the broncho-alveolar lavage fluid of patients with non-cardiogenic pulmonary edema,but not in those with cardiogenic edema

Leukotriene (LT) generation has been implicated in the pathogenesis of the acute respiratory distress syndrome, ARDS. In the present study, we analysed broncho-alveolar lavage fluids of patients on mechanical ventilation because of ARDS (17 samples taken from 9 patients) or because of cardiogenic edema (8 samples taken from 6 patients) and of healthy volunteers (10 samples from different donors). LTs were separated as methylated and non-methylated compounds using different HPLC procedures, and were identified by chromatographic mobility, on-line UV-spectrum analysis and post HPLC immunoreactivity. In the lavage samples of the healthy volunteers and the patients with cardiogenic edema, no LTs were detected by these techniques (detection limit congruent to 0.1-0.2 ng/ml lavage fluid). By contrast, in 15 out of 17 samples from patients with ARDS LTB4 or its metabolites 20-OH-LTB4 and 20-COOH-LTB4 were detected. The endproduct of omega-oxidation, 20-COOH-LTB4, represented the quantitatively predominant compound, detected in the range of 0.3-2.6 ng/ml perfusate. We conclude that the chemotactic agent LTB4 may be involved in the amplification of inflammatory events encountered in ARDS, and that the oxidized metabolites of LTB4 are particularly suitable for monitoring lung leukotriene generation under conditions of neutrophil efflux and oxidative stress.     

Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia

Glutathione concentrations were measured in rat bronchoalveolar lavage fluid (BALF) obtained from normal rats and rats exposed to a fraction of inspired oxygen (FiO2) of 0.8 for up to 5 days. We also perturbed rat lung glutathione concentrations by administering the compound diisopropylidene acetone (phorone) to a separate group of animals and correlated changes in BALF glutathione with changes in lung tissue glutathione. We found that reduced glutathione is present in normal rat BALF but glutathione disulfide is extremely low. Increases in lung tissue glutathione concentration and in BALF glutathione concentration occurred after 5 days of exposure to hyperoxia. Animals treated with phorone exhibited decreases in lung glutathione concentration two hours after dosing and increases in lung glutathione concentration 24 hours after dosing. Rat BALF obtained from phorone-treated animals at 2 or 24 hours after administration revealed that changes in BALF glutathione concentrations reflected changes in lung tissue glutathione concentration. The presence of glutathione in lung lavage fluid suggests that the compound could be playing an extracellular role in the lung, either as an antioxidant or as a coenzyme for other glutathione-related enzymatic reactions.     

支气管灌洗液肿瘤标志物联合检测对肺癌诊断价值探讨

目的　探讨支气管灌洗液 (BLF)中癌胚抗原 (CEA)、恶性肿瘤生长因子 (TSGF)及细胞角蛋白 19片段(CYFRA2 1 1)联合检测对肺癌的诊断价值。方法　标本取自 5 1例肺癌患者和 30例非肺癌患者的支气管灌洗液 ,CEA和CYFRA2 1 1测定采用放射免疫法 ,TSGF采用分光光度比色法检测。结果　肺癌组上述 3项指标均高于非肺癌组 (P <0 .0 0 1) ;肺癌组BLF中CEA、CYFRA2 1 1及TSGF的阳性率分别为 37.2 %、78.4 %及 88.2 % ,特异性分别为 83.3%、76 .4 %及 76 .4 % ,3项指标联合检测则特异性达 96 .7%。结论　BLF中CEA、CYFRA2 1 1及TSGF检测对肺癌的诊断有一定价值 ,3者联合检测有明显的互补性 ,可提高肺癌诊断的特异性及准确性     

Purine in bronchoalveolar lavage fluid as a marker of ventilation-induced lung injury.

OBJECTIVE: To investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Forty-two male Sprague-Dawley rats. INTERVENTIONS: Five groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid was collected in which both purine concentration (microM; mean +/- SD) and protein concentration (mg/mL; mean +/- SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student-Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 +/- 1.9 and 4.2 +/- 1.6, respectively) compared with Group 7/0 (0.4 +/- 0.1 [p < .05] and 0.4 +/- 0.2 [p < .001]) and controls (0.2 +/- 0.2 [p < .01] and 0.2 +/- 0.1 [p < .001]) and in Group 45/Na (5.8 +/- 2.5 and 4.2 +/- 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 +/- 0.3 and 0.4 +/- 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 +/- 1.6 and 2.7 +/- 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01). CONCLUSIONS: This study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end-expiratory pressure reduce protein infiltration and that positive end-expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation.     

白细胞介素32在肺癌患者支气管肺泡灌洗液及血清的表达

目的研究肺癌患者支气管肺泡灌洗液（BALF）和外周血清中白细胞介素32（interleukin-32,IL-32）表达及其临床意义。方法采用酶联免疫吸附测定（ELISA）技术测定40例肺癌患者及21例良性肺病变患者BALF和血清IL-32的浓度。结果①在BALF中肺鳞癌组患者IL-32（156.49±32.84）ng/L显著低于肺腺癌组（224.70±54.00）ng/L及肺良性病变组（219.06±67.82）ng/L（P〈0.05）,而血清IL-32浓度无论是肺鳞癌组（149.08±31.31）ng/L还是肺腺癌组（158.03±46.58）ng/L均低于肺良性病变组（188.11±45.98）ng/L（P〈0.05）;②Ⅳ期肺癌患者BALF中IL-32（221.43±53.02）ng/L高于Ⅲ期（157.68±37.56）ng/L和Ⅱ期（135.06±21.03）ng/L（P〈0.05）,而血清IL-32浓度尽管在Ⅱ期（122.84±25.23）ng/L、Ⅲ期（147.59±32.52）ng/L、Ⅳ期（158.60±39.01）ng/L肺癌患者逐渐升高,但三者浓度差异无统计学意义（P〉0.05）。结论 IL-32在肺良性病变及肺腺癌患者BALF中的高表达水平提示其可能参与肺部感染性疾病和肺腺癌的发病机制,肺癌患者BALF中IL-32浓度与肺癌TNM分期有关,表明它有可能成为肺癌的病程进展及预后不良一个指标。     

纤维支气管镜刷片与支气管肺泡灌洗液ThinPrep技术细胞学检测在肺癌诊断中的应用

目的探讨纤维支气管镜刷片(BWC)和支气管肺泡灌洗液(BALF)膜式液基细胞学检测(TCT)在肺癌诊断中的价值。方法收集同时进行纤支镜刷片和BALF TCT检查的肺癌病例325例,分析纤维支气管镜(BFS)和BALF TCT对肺癌诊断的敏感度和分型的准确性。结果在中央型肺癌的诊断中,BFS的敏感度87.2%,BALF的敏感度81.8%。在周围型肺癌的诊断中,BALF的敏感度54.8%,BFS的敏感度33.3%。细胞学分型诊断与组织学的符合率,在BFS中,鳞癌为93.5%,腺癌93.8%,小细胞癌96.2%。在BALF中,鳞癌为95.4%,腺癌95.2%,小细胞癌96.2%。结论由于肺癌的解剖部位的不同,在肺癌诊断中BALF和BFS的敏感度不同。如果两者结合,则可能提高肺癌的诊断率。     

Imipenem kinetics in serum, lung tissue and pericardial fluid in patients undergoing thoracotomy

Imipenem serum pharmacokinetics, lung tissue and pericardial fluid concentrations were measured in 10 patients undergoing thoracotomy, following a 1 g intravenous infusion of imipenem-cilastatin. The serum concentrations of imipenem 0.5 h and 4 h after the end of the 40 min infusion were 53.3 (+/- 16.7) and 2.0 (+/- 0.3) mg/l, respectively. The concentration of imipenem in lung tissue at 1 h was lower than in pericardial fluid and at 2.25 h the mean concentration of imipenem in pericardial fluid was 10.5 mg/l, vs. 0.28 mg/kg of lung tissue. Imipenem concentrations in pericardial fluid remained above 5 mg/l, well above the MIC for most pathogens, for 1 h whereas in pericardial fluid the concentration was 10.5 mg/l at 2.25 h.     

藻酸盐对家兔肺组织的免疫损伤作用

目的：建立藻酸盐免疫性肺炎动物模型，研究藻酸盐对肺组织的致病作用；以探讨细菌生物被膜对呼吸系统的致病机制。方法：本实验用乙醇沉淀法提取细菌藻酸盐；A组用生理盐水作对照，B组、C组分别用海藻藻酸盐、细菌藻酸盐免疫家兔。比较三组家兔的体温、血象及血循环免疫复合物(CIC)水平；比较支气管肺泡灌洗液(BALF)细菌计数；观察肺组织的病理改变。结果：两种藻酸盐免疫组家兔的血CIC水平皆较处理前及生理盐水对照组显著增高，BALF培养无细菌生长。经两种藻酸盐免疫后皆出现细支气管旁淋巴细胞浸润、淋巴小结形成及细支气管管腔狭窄等病理改变。结论：海藻藻酸盐和细菌藻酸盐都能导致家兔肺组织非感染性免疫损伤，其主要病理改变为细支气管旁淋巴细胞浸润及淋巴小结形成；这种免疫损伤是呼吸道生物被膜病的致病机制之一。     

Heterogeneity of alveolar surfactant in the rabbit: composition, morphology, and labelling of subfractions isolated by centrifugation of lung lavage

Rabbit alveolar saturated phosphatidylcholine (SPC) can be separated by differential and density gradient centrifugation of lung lavage into three fractions. One fraction ('B'), which is analogous to conventionally prepared alveolar surfactant, contains 46.0 +/- 5.9% (SD) of lavage SPC, and is made of large multilamellar vesicles or sheet-like structures. A second fraction ('C') does not sediment after centrifugation at 80 000 g for 90 min, contains 29.8 +/- 14.0% of lavage SPC, and a uniform population of small vesicles. This fraction incorporates 3H-palmitate administered intravenously with a small delay with respect to fraction 'B'. A third fraction ('D') contains almost all the cells of lavage and less than 5% of lavage SPC. We conclude that alveolar SPC consists of more than one compartment. The possible significance of isolated fractions is discussed.     

Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung,but not skin tissue

To investigate the mechanisms of anaphylactoid reactions to radiocontrast media, in vitro mediator release induced by three iodinated contrast agents was examined using peripheral blood basophils and mast cells purified from human lung parenchyma, heart, and skin tissues. Three iodinated contrast agents, sodium and meglumine salts of ioxaglic acid, sodium and meglumine salts of ioxithalamic acid, and ioversol, were incubated with basophils purified from peripheral blood and human mast cells isolated and purified from different anatomical sites. Release of preformed (histamine and tryptase) and de novo synthesized mediators (prostaglandin D₂ and leukotriene C₄) into the supernatans was determined at various contrast medium concentrations after incubation for 60 min. Ioxaglate (0.2–0.3 M), ioxithalamate (0.3–0.5 M), and to a lesser extent ioversol (0.3–0.5 M) induced histamine release from basophils in a concentration-dependent manner. All three induced the release of preformed mediators (histamine and tryptase) from human lung, but not from skin mast cells. They also induced histamine and tryptase release from human heart mast cells. However, they did not induce the de novo synthesis of leukotriene C₄ or prostaglandin D₂ from human basophils or any type of mast cell examined. Cross-linking of IgE by anti-IgE induced the release of leukotriene C₄ or prostaglandin D₂ from human basophils or mast cells. Mannitol, an osmotic stimulus, induced the release of histamine from human basophils, but to a lesser extent from mast cells. These results show that different contrast media can differ in their ability to release mediators from enriched preparations of human basophils and mast cells. The three contrast agents examined act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators, but not the de novo synthesis of chemical mediators. It may be useful to measure plasma tryptase levels to detect adverse reactions caused by iodinated radiographic contrast materials.     

Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury

Introduction

Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange

Methods

In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH₂O for 40 s with a constant positive end-expiratory pressure of 10 cmH₂O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung.

Results

Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO₂) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO₂, arterial partial carbon dioxide pressure (PaCO₂) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve.

Conclusion

A recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.     

Studies of cytokine levels in bronchoalveolar fluid lavage from patients with interstitial lung diseases

Cytokine levels in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia (n = 7), allergic alveolitis (n = 11), (cryptogenic) fibrosing alveolitis (n = 8), sarcoidosis (n = 10) were determined, as well as levels in control samples from healthy non-smoking volunteers (n = 11). Fibronectin levels were increased in all the patient categories, the highest absolute levels of fibronectin (100-fold increase) being found in eosinophilic pneumonia and allergic alveolitis. TGF-beta (transforming growth factor-beta) was significantly elevated in allergic alveolitis only. There was a significant difference between allergic alveolitis on the one hand and both sarcoidosis and fibrosing alveolitis on the other. Tumour necrosis factor-alpha (TNF-alpha) was significantly increased in eosinophilic pneumonia and allergic alveolitis; allergic alveolitis and fibrosing alveolitis differed significantly in this respect. Platelet-derived growth factor-BB (PDGF-BB) levels were significantly elevated in allergic alveolitis and fibrosing alveolitis. It was found that the level of PDGF-BB was significantly decreased in the case of sarcoidosis, with no overlapping with allergic alveolitis or fibrosing alveolitis. Interferon-gamma (IFN-gamma) was decreased in all patient categories. A significant difference in extent of the decrease was found between allergic alveolitis and sarcoidosis. The interstitial lung diseases thus differed in the pattern of cytokines expressed, indicating that these cytokines could well be a part of the pathogenic process, and also that the measurement of cytokine levels could be diagnostically useful.