Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma

Bonnans, Caroline; Vachier, Isabelle; Chavis, C.; Godard, P.; Bousquet, Jean; Chanez, Pascal

doi:10.1164/rccm.200201-053oc

Cited by 123 publications

(119 citation statements)

References 39 publications

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“…Lipoxins are produced in human asthmatics and potently attenuate human monocyte inflammatory responses (40). Moreover, ATLa potently attenuates airway hyper-reactivity and eosinophilia in murine allergic airway inflammation via multipronged suppression of inflammatory mediators (41).…”

Section: Discussionmentioning

confidence: 99%

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Schottelius¹,

Giesen²,

Asadullah³

et al. 2002

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Schottelius¹,

Giesen²,

Asadullah³

et al. 2002

The Journal of Immunology

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“…Interestingly, lipoxin levels were found to be higher in subjects with mild asthma compared with individuals with severe asthma [36]. Indeed synthetic lipoxin analogues have been shown to block the development of allergen-induced airway hyperresponsiveness and prevent expression of IL-5, IL-13, eotaxin and prostanoids [37].…”

Section: Induction Of Endogenous Immunomodulatory Lipids By Pathogensmentioning

confidence: 99%

Control of inflammatory diseases by pathogens: lipids and the immune system

Kleij

Yazdanbakhsh

2003

Eur J Immunol

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Inflammatory diseases such as asthma and diabetes are rising in industrialized countries and the modern lifestyle that is associated with lower exposure to microbes has been held responsible for the increasing prevalence of these diseases. Several studies have shown an inverse association between pathogen-exposure and allergy or autoimmunity. The mechanisms behind such protective effects have been investigated at the epidemiological, cellular and molecular level and have provided data on the ability of lipids either derived directly from pathogens or up-regulated as a result of an infection to down-regulate immune responses and thereby control inflammatory diseases. In this mini-review, recent findings and new concepts relating to the immunosuppressive effects of endogenous lipids and those encountered upon exposure to bacteria, protozoa and particularly helminths are discussed. The overview focuses on the modulation of interactions between the antigen-presenting compartment and T cells to start an anti-inflammatory "program" with potential to regulate disease processes. PGJ 2 Lyso-PA: Lysophosphatidic acid Lyso-PC: Lysophosphatidylcholine Lyso-PS: Lysophosphatidylserine LXA4: Lipoxin A4 TLR2: Toll-like receptor 2 Treg cell: Regulatory T cell The inverse relationship between infections and allergiesThe prevalence of allergies has increased significantly over the last few decades, particularly in industrialized countries. Within these countries, a negative association has been found between certain childhood infections and allergic diseases [1,2]. Lifestyles such as anthroposophy or traditional farming -thought to be associated with higher exposure to pathogens or pathogen-derived products -have been shown to be protective against atopic disorders [3,4]. Furthermore, in low-income countries, where exposure to pathogens is higher, the prevalence of allergy is often lower than in industrialized countries [5]. Studies examining the relationship between allergies and parasitic infections in areas where transmission is intense have revealed that children with chronic helminth infections have a lower risk of wheeze or of skin-prick-test positivity for house-dust mite [6,7].The question of how infections can prevent allergies has received much attention in the last few years. Although many bacteria and viruses induce Th1 responses, which in turn may prevent the development of Th2 responses, helminths -which are potent Th2 inducers -are surprisingly also protective [7]. This has led to the question of what additional mechanisms, acting downstream of the induction/initiation phase, suppress allergic inflammation. Such mechanisms downstream of T cell polarization would work to protect not only from Th2 inflammation but also from Th1 inflammation, and their absence would explain the concurrent rise at the population level in allergies (Th2 diseases) and autoimmunities (often Th1 diseases) [8]. The possibility that immunosuppressive regulatory responses stimulated during repeated/intense exposure to pathogens or pathogenderi...

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“…LXs may also increase NK cell-mediated apoptosis of both eosinophils and neutrophils (5). Thus, LXs exhibit the anti-inflammatory properties of montelukast and corticosteroids and have been indicated as a potential endogenous 'braking signal' in the inflammatory process, and these properties indicate the potential superiority of LXs in the treatment of asthma (5,17,18,22). Indeed, the biological activity of the LXs in asthma has been defined over the past two decades.…”

Section: Introductionmentioning

confidence: 99%

Pilot application of lipoxin A4 analog and lipoxin A4 receptor agonist in asthmatic children with acute episodes

Kong

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have demonstrated that lipoxin A 4 (LXA 4 ) analogs blocked both airway hyper-responsiveness and pulmonary inflammation in a murine model of asthma. The present pilot study investigated the initial efficacy and safety of inhaled 5(S),6(R)-LXA 4 methyl ester and BML-111, a LXA 4 agonist, in the treatment of asthmatic children with acute episodes. A total of 50 asthmatic children diagnosed with acute moderate asthma were randomly assigned into groups and subjected to an inhalation challenge with pulmicort (n=10), ventolin (n=10), 5(S),6(R)-LXA 4 methyl ester (n=10), BML-111 (n=10) or normal saline as a placebo (n=10). Pulmonary function was assessed prior to and following the challenge. Acute toxicity and safety of the inhaled 5(S),6(R)-LXA 4 methyl ester and BML-111 in normal BALB/c mice were investigated prior to the current pilot study conducted in patients. Following the inhalation challenge, pulmonary function parameters in all groups with the exception of the normal saline-treated group indicated an improvement. The efficacies of 5(S),6(R)-LXA 4 methyl ester and BML-111 were superior to the efficacy of pulmicort but reduced when compared to the efficacy of ventolin with regard to the improvement of pulmonary function following the inhalation challenge. No clinical adverse events were observed in the enrolled patients. All safety parameters in the full blood counts, routine urine and feces examination, electrocardiogram and liver and kidney function tests at baseline and the end of the current study were within normal limits for all patients. No significant differences in kidney or liver function tests were observed in mice treated with 5(S),6(R)-LXA 4 methyl ester and BML-111. Light and electron microscopy demonstrated no airway epithelium or alveolar epithelial cell damage in the treated mice. The present preliminary study of a small sample demonstrates the initial efficacy and safety of inhaled 5(S),6(R)-LXA 4 methyl ester and BML-111 in the treatment of asthmatic children with acute moderate episodes, and suggests that an inhaled LXA 4 analog and LXA 4 receptor agonist may exhibit potential as a novel therapeutic strategy for asthma.

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Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma

Cited by 123 publications

References 39 publications

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

Control of inflammatory diseases by pathogens: lipids and the immune system

Pilot application of lipoxin A4 analog and lipoxin A4 receptor agonist in asthmatic children with acute episodes

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