Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation

Abstract

Interleukin-23 (IL-23) is integral to the pathogenesis of chronic inflammation. Resolution of acute inflammation is an active process mediated by specific signals and mediators, such as resolvin E1 (RvE1). Here, we provide the first evidence that RvE1, in nanogram quantities, promotes resolution of inflammatory airway responses in part by directly suppressing IL-23 and IL-6 production in the lung. Also contributing to the pro-resolving effects of RvE1 treatment were increased concentrations of interferon-γ in the lungs of RvE1-treated animals. These findings point to a pivotal role of IL-23 and IL-6-which promote survival and differentiation of T H -17 cells-in maintaining inflammation, and uncover an RvE1-initiated resolution program for allergic airway responses.

Resolvin E1 Improves Tear Production and Decreases Inflammation in a Dry Eye Mouse Model

“…32 The now observed marked attenuation of the influx of T cells and macrophage/dendritic cells is in agreement with observations in different models that show RvE1-mediated prevention of leukocyte influx following a proinflammatory insult. 7,9,10,33,34 Resolvin-mediated regulation of leukocyte migration is now extended to the DE mouse model, which, in contrast to previous immune activation models used for exploring the effects of RvE1, is more a stress-activation-dependent model. It should be noted that corneal T-cell infiltration following desiccating stress has been mainly studied in C57BL/6 mice, which show predominantly Th-1 infiltration, whereas a Th-2 response is predominant in balb/c mice, which were used in these experiments.…”

“…8 Since then, resolvins have been demonstrated to exert broad regulatory actions that would favor their use as therapeutics in both acute and, more importantly, chronic inflammation. RvE1 is now demonstrated to stimulate the resolution of inflammatory airway responses in the lung by suppressing interleukin (IL)-23, IL-17, and IL-6 production 9 ; increase survival and reduce tissue inflammation in a mouse model of colitis 10 ; and reduce retinal neovascularization in an animal model of oxygen-induced retinopathy. 11 The endogenous formation of resolvins may also explain the recently published data from the longitudinal women's health study in which women on a high daily diet of omega-3 polyunsaturated fatty acids had a lower frequency of DE symptoms than those on a more common regimen.…”

Fish Oil Metabolites: Translating Promising Findings from Bench to bedside to Reduce Cardiovascular Disease

“…Using this study as an example, anticipated human equivalent doses should range from 0.01 to 0.1 mg/kg. However, in another study investigating the effects of RvE1 in asthma mouse models, a reduction in leukocyte bronchoalveolar lavage fluid, airway mucus, and airway hyperactivity was pronounced with intravenous doses ranging from 50 to 200 ng/mouse [43]. At same time, other successful studies have used intrathecal RvE1 and RvD1 at doses of 10 ng/mouse in order to investigate their effects in acute and persistent pain [44].…”

Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

“…They were challenged on both sides of each ear with 20 µl of 0.3% (wt/vol) DNFB 5 d after sensitization. RvE1 (200 ng/mouse in 200 µl of 1.8% ethanol in PBS) or its vehicle (200 µl of 1.8% ethanol in PBS) was applied 1 d before and on the day of sensitization or 5 d after sensitization via intravenous injection, according to a previous study (Haworth et al, 2008) with some modifications. Ear thickness change was measured for each mouse before and 24 and 48 h after the challenge using a thickness gauge (Teclok), and the difference was expressed as ear swelling.…”