The anesthetic agent sevoflurane attenuates pulmonary acute lung injury by modulating apoptotic pathways.

The objective of this study was to evaluate lung protection by the volatile anesthetic sevoflurane (SEVO), which inhibits apoptosis. Male Sprague-Dawley rats (250-280 g; n=18) were randomly divided into three groups. The LPS group received 5 mg/kg endotoxin (lipopolysaccharide), which induced acute lung injury (ALI). The control (CTRL) group received normal saline and the SEVO group received sevoflurane (2.5%) for 30 min after ALI was induced by 5 mg/kg LPS. Samples were collected for analysis 12 h after LPS. Lung injury was assessed by pathological observations and tissue wet to dry weight (W/D) ratios. Apoptotic index (AI) was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and electron microscopy. Caspase-3 and cleaved-caspase-3 protein levels were determined by immunocytochemistry and western blotting, respectively. Bcl-xl levels were measured by western blotting and Bcl-2 levels by quantitative real-time polymerase chain reaction and western blotting. In the LPS group, W/D ratios, AI values, caspase-3 and cleaved-caspase-3 levels were significantly higher than in the CTRL group and lung injury was more severe. In the SEVO group, W/D ratios, AI, caspase-3 and cleaved-caspase-3 were lower than in the LPS group. Bcl-2 and Bcl-xl expression were higher than in the LPS group and lung injury was attenuated. Sevoflurane inhalation protected the lungs from injury by regulating caspase-3 activation and Bcl-xl and Bcl-2 expression to inhibit excessive cell apoptosis, and such apoptosis might be important in the pathogenesis of LPS-induced ALI.

Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis.

OBJECTIVE: To determine whether abnormalities of cellular immunity are present and linked to early wheezing after bronchiolitis. METHODS: We prospectively studied 26 infants hospitalized for a first episode of bronchiolitis and without any prior immune, cardiac, or respiratory disease. Blood was obtained at the time of enrollment and 5 months later for the assessment of the total cellular and differential counts, CD4+ (helper) and CD8+ (suppressor/cytotoxic) lymphocytes, and the activation markers CD23 (low-affinity immunoglobulin E receptor) and CD25 (interleukin-2 (IL-2) receptor). The cytokines interferon gamma (T-helper (TH) type-1 cytokine) and IL-4 (TH-2) were measured in plasma and in vitro after stimulation with IL-2 or with the house-dust mite (Dermatophagoides farinae) antigen. A daily log of episodes of wheezing was kept by parents after discharge. RESULTS: We found an increase in blood eosinophils, an increased percentage of CD4+, CD25+, and CD23+ lymphocytes in subjects at 5 months compared with the time of bronchiolitis and with healthy subjects of the same age (p < 0.05). Plasma IL-4 levels, although not different from those of healthy subjects, also increased significantly. Peripheral blood lymphocytes from infants who wheezed produced more IL-4 in vitro, 5 months after bronchiolitis, in response to D. farinae antigen. In babies who wheezed, a positive correlation was found between the total number of days that wheezing occurred and the blood eosinophil count. Babies who wheezed more often (> 20 days) had more peripheral blood basophils and eosinophils, and peripheral blood lymphocytes obtained from these subjects at the time of bronchiolitis produced less interferon gamma on stimulation with IL-2. CONCLUSIONS: Bronchiolitis is followed by activation of cellular immunity, and early wheezing in infants is associated with a TH-2 response.