Role of interleukin-6 in murine airway responses to ozone

Abstract

This study sought to examine the role of interleukin-6 (IL-6) in ozone (O3)-induced airway injury, inflammation, and hyperresponsiveness (AHR). Subacute (72 h) exposure to 0.3 ppm O3significantly elevated bronchoalveolar lavage fluid (BALF) protein, neutrophils, and soluble TNF receptors (sTNFR1 and sTNFR2) in wild-type C57BL/6 (IL-6+/+) mice; however, all four outcome indicators were significantly reduced in IL-6-deficient (IL-6−/−) compared with IL-6+/+mice. Acute O3exposure (2 ppm for 3 h) increased BALF protein, KC, macrophage inflammatory protein(MIP)-2, eotaxin, sTNFR1, and sTNFR2 in IL-6+/+mice. However, MIP-2 and sTNFR2 were not significantly increased following O3exposure in IL-6−/−mice. Increases in BALF neutrophils induced by O3(2 ppm for 3 h) were also significantly reduced in IL-6−/−vs. IL-6+/+mice. Airway responsiveness to methacholine was measured by whole body plethysmography before and following acute (3 h) or subacute (72 h) exposure to 0.3 ppm O3. Acute O3exposure caused AHR in both groups of mice, but there was no genotype-related difference in the magnitude of O3-induced AHR. AHR was absent in mice of either genotype exposed for 72 h. Our results indicate that IL-6 deficiency reduces airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following acute high dose and/or subacute low-dose O3exposure, but has no effect on O3-induced AHR.

Airway inflammation is augmented by obesity and fatty acids in asthma

“…It is plausible that systemic inflammation does affect the airways. Indeed genetically IL-6-deficient, ozoneexposed mice have reduced airway neutrophils [29], while elevated CRP is associated with accelerated lung function decline independent of BMI [30]. In this study, asthma independently increased plasma levels of IL-6 by ,50%.…”

Role of cathepsin S in ozone-induced airway hyperresponsiveness and inflammation

“…The increased levels of IL-6 in BALF following ozone exposure were accompanied by simultaneous increases in IL-6 mRNA in lung tissue (24;25), indicating that changes in BALF concentration of IL-6 were also reflected in the lung expression of IL-6. However, although BALF neutrophils were reduced following 3ppm exposure to ozone for 2 hours in IL-6 knockout mice compared to IL-6 transgenic mice, AHR was not affected (26), indicating a dissociation of IL-6 expression and AHR. Similar dissociation between AHR and TNFα expression has been reported.…”

Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13

“…Previous studies have shown that bradykinin-induced increase in IL-6 protein and mRNA is inhibited by IL-13 in human ASM cells and that IL-6 expression was also found to be bradykinin B 2 receptor-dependent [43]. Interestingly, IL-6 has been shown to play a pro-inflammatory role in ozone-induced inflammation [44].…”