Repeated inhalation of sevoflurane inhibits airway inflammation in an OVA-induced mouse model of allergic airway inflammation : Sevoflurane and lung inflammation

Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.

The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study. As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.). Copyright 2006 Massachusetts Medical Society.

Transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) are regulatory cytokines with pleiotropic roles in the immune system. The prominent function of TGF-beta is to maintain T cell tolerance to self or innocuous environmental antigens via its direct effects on the differentiation and homeostasis of effector and regulatory T cells. A critical route for the regulation of T cells by TGF-beta is via activation of a T cell-produced latent form of TGF-beta1 by dendritic cell-expressed avbeta8 integrin. IL-10 operates primarily as a feedback inhibitor of exuberant T cell responses to microbial antigens. T cells are also the principal producers of IL-10, the expression of which is regulated by IL-27, IL-6, and TGF-beta. The collective activity of TGF-beta and IL-10 ensures a controlled inflammatory response specifically targeting pathogens without evoking excessive immunopathology to self-tissues.