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Increased nitrogen monoxide (NO) concentrations change leukocyte function under a multitude of experimental conditions. NO inhalation is an experimental treatment for lung failure and exposes leukocytes to increased NO concentrations during passage through the lungs. To investigate whether short-term NO inhalation induces lasting changes in the function of circulating human leukocytes, venous blood samples were drawn from eight healthy male volunteers before and at the end of a 35-min period of breathing 40 ppm NO in 30% O(2). The leukocytes in the samples were subsequently analyzed for NO-induced changes in expression of cell surface molecules, generation of reactive oxygen species (ROS), and cytokine production by flow cytometry and ELISA techniques. The results were (1) NO inhalation changed neither the baseline nor the Escherichia coli lipopolysaccharide (LPS)-induced expression of the cell adhesion molecules CD11a, CD11b, CD11c, and CD62L (l-selectin) on neutrophilic granulocytes (PMN) or monocytes (Mo). The expression of CD14 and HLA-DR was also unchanged. (2) The generation of ROS in response to activation with phorbol myristate acetate increased in PMN after NO inhalation; an increase in Mo did not reach significance. (3) Baseline and LPS-stimulated production of IL-1beta decreased after NO inhalation, while the LPS-stimulated production of TNF-alpha increased. No changes in IL-6 production were detected., (Copyright 2000 Academic Press.)

Background: Acute fire smoke inhalation injury involves inflammatory mediators whose roles are poorly understood. We carried out a prospective observational study of fire smoke victims to identify clinical and biochemical markers that may predict pulmonary dysfunction and investigated possible correlations between dysfunction and cytokines in bronchoalveolar lavage (BAL) fluid and blood.Methods: Forty patients with respiratory and/or neurological symptoms following acute fire smoke inhalation had pulmonary function tests and blood gas analyses performed on admission, at discharge, and after 3 months. Cytokines were measured using BioPlex/XMap technology.Results: On admission, 30 (75%) patients had dyspnea. Patients presenting with bronchial wheezing (n = 14) had significantly lower PEF (201 l/min, 82-360) than non-wheezing patients (406 l/min, 100-683) (n = 16, P = 0.03). Bronchial wheezing predicted need for ICU treatment with OR = 93.3 at 95% CI (P < 0.001) and was associated with gas exchange impairment, with mean pa O2 /FiO2 ratio 34.4 (11.8-49.8) kPa on admission and 21.3 (8.3-44.5) kPa 48 h later. Blood HbCO also predicted ICU treatment, with OR = 1.58 at 95% CI (P < 0.001). Serum CRP, IL-6, IL-8, and MCP-1 were significantly higher in wheezing patients after 12-24 h compared with non-wheezing patients and study controls. Cytokine levels were still elevated after 3 months. BAL fluid had significantly higher levels of IL-8, MCP-1, IL-1β, and G-CSF compared with healthy controls.Conclusion: In victims of fire smoke inhalation, pulmonary wheezing predicts inflammation, pulmonary dysfunction, respiratory failure, and need for intensive care. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that alterations in blood glucose and/or insulin levels modify the inflammatory response. The purpose of this study was to elucidate whether increased levels of glucose and/or insulin influence the activation pattern of blood leucocytes and their production of cytokines in vitro. Methods: Venous blood was obtained from eight healthy male volunteers after an overnight fast. Glucose and/or insulin were added to aliquots of whole blood to increase the blood glucose concentration by 5 or 20 mmol/l and/or the insulin concentration by 6 or 30 nmol/l, respectively, before stimulation with E. coli lipopolysaccharide (LPS) at concentrations of 10, 100 or 1000 ng/ml. The samples were subsequently incubated at 37 °C for 6 h before cytokine measurements. After centrifugation the levels of interleukins (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α were measured in plasma using enzyme-linked immuno-sorbent assays. The results were compared with cytokine levels in parallel control samples to which only identical amounts of LPS were added. Results: The LPS-stimulated production of IL-1β was significantly reduced by on average 26% in samples to which glucose 20 mmol/l was added; addition of insulin and/or glucose 5 mmol/l had no apparent effect on the IL-1β production at any LPS concentration. The levels of IL-6, IL-8, IL-10 and TNF-α were not manifestly altered by addition of glucose and/or insulin at any LPS concentration. Conclusion: A substantial increase in blood glucose concentration changed the IL-1β production, but not the production of other cytokines, in response to LPS stimulation. [ABSTRACT FROM AUTHOR]