Acute Respiratory Distress Syndrome: Basic And Clinical Study

Objective: The aim of this study was to investigate:(1) the influence of nitric oxide (NO) and interleukin (IL)-10 on the proinflammatory effect of alveolar macrophage (AM)(2) the effects of studying agents on the inflammatory and anti-inflammatoryresponse of AMTripterygium Wilfordii Hook (T4)Dexamethasone (Dex)S-methylisothiourea sulfate (SMT), an inducible nitric oxide synthase (iNOS) inhibitor(3) the effects of the above agents on lipopolysaccharide (LPS) - induced lunginjury(4) the mortality and related risk factors in critically ill patients with acuterespiratory distress syndrome (ARDS)Method: AM was obtained by bronchoalveolar lavage. The cytokine levels in bronchoalveolar lavage fluid (BALF), plasma and cell cultural supernatants were measured by ELISA. In animal model, the degree of LPS-induced acute lung injury was evaluated by the wet and dry weight ratio of lung. The expression and stability of cytokines and iNOS mRNA were assessed by RT-PCR. In a retrospective cohort study, the factors causing and contributing to death in patients with ARDS were analyzed by stepwise logistic regression analysis. Results(1) LPS stimulation of cultured AMs led to substantial production of tumor necrosis factor (TNF) α , IL-1β and IL-6 and NO. Inhibition of NO production by SMT increased IL-1β and IL-6, whereas TNFa concentration remained unchanged.In contrast, S-nitroso-N-acetyl-D,L-penicillamines (SNAP), a NO donor, exerted dose-dependent inhibition of IL-1β and IL-6 production in LPS-stimulated AMs. Addition of recombinant IL-10 reduced LPS-induced TNF α , IL-1β , and IL-6, while IL-10 monoclonal antibody increased proinflamatory cytokines.