Marked connective tissue remodelling involves both destruction and repair in inflammatory lung diseases. Throughout the remodelling event, it was reasoned that alveolar macrophages may release substances similar to those produced by blood monocyte-macrophages that affect fibroblast functions, ie, the interleukin 1 family of monokines (or cytokines). We have examined human alveolar macrophage cultures obtained after bronchoalveolar lavage of freshly excised lungs from heavy smokers with bronchial carcinoma. Crude culture media contained fibroblast proliferative activity and collagenase- and PGE2- production-stimulating activity. The main peak of these biological activities was located around approximately 18 kilodaltons (kD) on gel filtration chromatography. Resolution of this peak by high performance liquid chromatography showed the presence of three distinct peaks, with quantitative and qualitative differences in biological activities. This suggests the presence of heterogeneous factors.

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Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropamide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV, was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV,; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, ,B endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. It has recently been reported that endogenous peptides with opiate like activity, such as enkephalin, may mediate the asthma and facial flush observed in some diabetics treated with chlorpropamide when they drink alcohol.7 Both sodium cromoglycate and the specific opiate antagonist were able to prevent the asthmatic reaction, which could be reproduced by an enkephalin analogue with opiate like activity.8 It is also known that various types of exercise increase plasma concentrations of endogenous opioids such as f endorphin.9' " The present study was therefore undertaken to investigate whether exercise induced asthma might also be related either to an increase in circulating opioid peptide-f endorphin or metenkephalin or both-or to increased sensitivity to endogenous opiates, or to both. For this purpose plasma f endorphin and met-enkephalin immunoreactivities were measured in asthmatic patients Address for reprint requests: Dr RC Gaillard, Clinique m&dicale, Hopital cantonal universitaire, 1211 Geneva 4, Switzerland. Accepted 23 October 1985 breathing cold, dry air during exercise. In four of these asthmatic subjects the effect of naloxone perfusion on the respiratory variables during exercise induced asthma was also measured. Methods SUBJECTS AND PROTOCOLFive patients suffering from exercise induced asthma and five healthy subjects (three men and two women in both cases) were studied. The subjects of the two groups did not differ in age, weight, or body surface area. The mean ages of the asthmatic and control subjects respectively were 29.2 (SE 4.2) and 30.3 (2.8) years, and the mean weights 65 (4.7) and 67.2 (3.6) kg. The mean body surface area was 1.72 (0.1) m2 for the asthmatic patients and 1.82(0.6) m2 for the control subjects. The patients were not receiving local or systemic corticosteroid treatment. The controls had not smoked or taken any medication or alcohol for at least 24 hours before the experiment.The study p...

To better understand how the activity of inflammatory cells collected by bronchoalveolar lavage (BAL) could affect the outcome of granulomatous and fibrotic pulmonary diseases, we studied secretory products and messenger ribonucleic acid (mRNA) expression for certain cytokines of BAL cells in 10 controls, 14 patients with interstitial pulmonary fibrosis (IPF) and 22 patients with sarcoidosis. We assayed the activity of 48 h conditioned media for: 1) their biological action on fibroblast proliferation and prostaglandin E2 (PGE2), collagenase and collagen production by fibroblasts; 2) TNF alpha levels by bioassay and radioimmunoassay; 3) interleukin 1 (IL-1) alpha and beta and beta levels by solid phase enzyme immunoassay (EIA); 4) tumor necrosis factor (TNF) and IL-1 inhibitory activity. We also measured, in freshly isolated BAL cells: 1) mRNA levels for IL-1 alpha and beta and TNF alpha; 2) cell-associated IL-1 alpha and beta by EIA. The only difference found in the assessment of the biological activity of BAL cells conditioned medium was an increase in fibroblast proliferation in sarcoidosis vs IPF patients. The IL-1 alpha and beta, and TNF alpha contents of conditioned media were similar in the three groups. Inhibitory activity against IL-1 and TNF alpha was found in a few patients. Further analysis revealed two peaks of inhibitory activity against IL-1 (20-25 kD and 35-40 kD), as well as a distinct TNF alpha inhibitory activity which could be retained on a TNF alpha-binding affinity column. No mRNA expression for TNF alpha was found in freshly isolated BAL cells, whereas very variable levels of IL-1 alpha and beta mRNA levels were detected in the three groups. Because of these variable results of differences in functional state between freshly isolated and cultured BAL cells, and of the presence of inhibitory substances against IL-1 and TNF alpha, it is unlikely that the development of fibrosis could be ascribed to a single disorder or abnormality.

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