The concentrations of hyaluronan (HA) were measured in bronchoalveolar lavage (BAL) fluid and serum from 12 patients with adult respiratory distress syndrome (ARDS). The median BAL fluid HA concentration was 353 micrograms/L, about six times higher than that seen in control patients (p less than 0.001). The median serum HA value was 619 micrograms/L, which was a 30-fold increase compared with that in the control patients (p less than 0.001). Another connective tissue component, type III procollagen peptide, was not recovered in significant amounts during lavage in patients with ARDS, but it appeared in the bloodstream in increased concentrations (p less than 0.001). Obtained recovery of HA during lavage of patients with ARDS cannot be explained by an enhanced passive leakage from the bloodstream because of increased alveolar-capillary permeability, but rather could reflect a mobilization of HA from lung interstitial tissue because of hydrostatic mechanisms. Alternatively, the appearance of HA in the alveolar space in ARDS might reflect an enhanced lung synthesis of HA. An increased HA production can possibly be mediated, directly or indirectly, by activated complement components, since a significant relationship was seen between increased plasma concentrations of C3a des Arg and BAL fluid HA (r = 0.61; p less than 0.05). The observed accumulation of HA in the small airways in ARDS may be expected to immobilize water and thereby contribute to the interstitial and alveolar edema. The inverse correlation (r = 0.71; p less than 0.01) seen between BAL fluid HA and pulmonary oxygenation index (PaO2/inspired oxygen fraction) supports such a hypothesis.

Objectives-To test the hypothesis of a diurnal variation in circulating levels of interleukin-6 (IL-6) and/or tumour necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis and other inflammatory connective tissue diseases.

The connective tissue components hyaluronan (hyaluronic acid) and type III procollagen peptide were measured in bronchoalveolar lavage fluid in 22 patients with idiopathic pulmonary fibrosis and 21 healthy control subjects. The patients with idiopathic pulmonary fibrosis had higher concentrations of hyaluronan (median 46 Mg/l) and type III procollagen peptide (median 0-45 jg/l) than the healthy controls (9 and < 0-2 yg/l; p < 0001). The patients had normal serum concentrations of hyaluronan and of the procollagen peptide, and albumin concentrations in lavage fluid similar to those of the control subjects. Neutrophil and lymphocyte counts in lavage fluid were increased on average 10 and two fold respectively in the patients with idiopathic pulmonary fibrosis and both correlated with the amount ofhyaluronan recovered (p < 0-05). An inverse correlation was seen between the transfer factor for carbon monoxide and hyaluronan concentrations in lavage fluid in the patients (p < 0-05). Deterioration in lung function and radiographic progression were seen over six months in 12 of the patients. These patients had higher lavage fluid concentrations of hyaluronan and type III procollagen peptide than the patients whose disease was stable (p < 0-01). Increased synthesis of hyaluronan and type III procollagen peptide in lung parenchyma may reflect activation or proliferation (or both) of pulmonary fibroblasts in idiopathic pulmonary fibrosis and seems to be linked to the severity and activity of the lung disease.

Gerdin B, Hällgren R (University Hospital, Uppsala, Sweden). Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 49–55. An increased tissue accumulation of HYA occurs in several human and experimental inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary fibrosis and farmer's lung in man, and experimental bleomycin‐induced lung damage in rats. Graft rejection in man and rats, experimental myocarditis in mice and myocardial infarction in rats follow the same pattern. Increased amounts of HYA also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A transient accumulation of HYA is seen in wound healing, which is more sustained in fetuses. An increased accumulation of water and presentation of ligands for receptors on inflammatory cells are two consequences of the HYA accumulation.

By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in the lungs of rats at different times (4, 10, and 20 days) after bleomycin injury. Four days after an intratracheal injection of bleomycin, HA was accumulated in the edematous alveolar septa of the focal areas with lung tissue injury. An interstitial cellular infiltrate of mainly lymphocytes was present. In normal rat lung, HA was not seen in the alveolar tissue but confined to peribronchial and perivascular spaces. Ten and twenty days after bleomycin administration, increasing numbers of macrophages were apparent in the alveolar space. Proliferating fibroblasts and deposition of collagen in the alveolar tissue were observed while the diffuse HA accumulation was becoming less prominent in the alveolar interstitial tissue. HA was more distinctly located in the surroundings of proliferating fibroblasts. A few scattered alveolar macrophages showed a positive staining for HA. An increased water content of the lung was most apparent 4 days after bleomycin administration. The accumulation of HA, a glycosaminoglycan with unique qualities to immobilize water, in the alveolar interstitium suggests a role for HA in the alveolar interstitial edema. The appearance of HA in alveolar macrophages might indicate that macrophage phagocytosis contributes to the elimination of HA from inflamed lung tissue.