Neutrophils have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). We have measured concentrations of the neutrophil attractant interleukin-8 in blood and bronchoalveolar lavage fluid (BAL) from patients at risk of ARDS. We studied 29 patients from three groups at risk of developing ARDS: multiple trauma (n = 16), perforated bowel (n = 6), and pancreatitis (n = 7). ARDS developed in 7 of these patients. Interleukin-8 in BAL and blood samples taken on initial hospital presentation was measured by a sandwich enzyme-linked immunosorbent assay. The mean BAL interleukin-8 concentration was significantly higher for the patients who subsequently progressed to ARDS than for the non-ARDS group (3.06 [SE 2.64] vs 0.053 [0.010] ng/mL, p = 0.0006). There was no difference between the groups in plasma interleukin-8 (6.23 [2.60] vs 5.12 [2.22] ng/mL, p = 0.31). Immunocytochemistry suggested that the alveolar macrophage is an important source of interleukin-8 at this early stage in ARDS development. This study provides evidence of a relation between the presence of interleukin-8 in early BAL samples and the development of ARDS. The early appearance of interleukin-8 in BAL of patients at risk of ARDS may be an important prognostic indicator for the development of the disorder and reinforces the likely importance of neutrophils and the effects of their accumulation and activation in the pathogenesis of many cases of ARDS.

Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.

Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin.

Bronchoalveolar lavage fluid concentration of anti-interleukin-8:interleukin-8 complexes may serve as a marker of disease progression in patients at risk for acute respiratory distress syndrome.