Role of imbalance of eicosanoid pathways and staphylococcal superantigens in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a multifactorial disease of the upper airways with a high prevalence (approximately 11%) in the general population. Different immune and inflammatory mechanisms are involved in its pathogenesis. Alterations in the arachidonic acid pathway (leading to an imbalanced production of eicosanoids) have been linked to the pathophysiology of different diseases especially nasal polyposis, asthma, and aspirin‐exacerbated respiratory disease. Furthermore, viral and bacterial infections have been identified as important factors amplifying the pro‐inflammatory reactions in these pathologies. This review summarizes the impact of an imbalance in the eicosanoid pathway and the effect of Staphylococcus aureus enterotoxins on the regulation of the pro‐inflammatory network in CRS and their translation into disease severity.     

Periodontal disease: modulation of the inflammatory cascade by dietary n‐3 polyunsaturated fatty acids

Periodontal disease, including gingivitis and periodontitis, is caused by the interaction between pathogenic bacteria and the host immune system. The ensuing oxidative stress and inflammatory cascade result in the destruction of gingival tissue, alveolar bone and periodontal ligament. This article reviews the underlying mechanisms and host–bacteria interactions responsible for periodontal disease and evidence that nutritional supplementation with fish oil may provide a protective effect. Historical investigations of diet and disease have highlighted an inverse relationship between ingestion of fish oil, which is high in n‐3 polyunsaturated fatty acids, and the incidence of typical inflammatory diseases such as arthritis and coronary heart disease. Ingestion of n‐3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, results in their incorporation into membrane phospholipids, which can alter eicosanoid production after stimulation during the immune response. These eicosanoids promote a reduction in chronic inflammation, which has led to the proposal that fish oil is a possible modulator of inflammation and may reduce the severity of periodontal diseases. Tentative animal and human studies have provided an indication of this effect. Further human investigation is needed to establish the protective effects of fish oil in relation to periodontal disease.     

Effect of nicotine on arachidonic acid metabolites and epithelial parameters in rat oral mucosa

This study examined the effects of nicotine on oral mucosal levels of eicosanoids and on histologic parameters, including keratinocyte proliferation. Surgically-created canals in the mandibular lips of 20 male Sprague Dawley rats received either nicotine or saline in a cotton pellet twice daily for six weeks. Thromboxane B₂(T×B₂) levels were depressed ( P < 0.05) in nicotine treated tissues compared to saline treatment (5.8±1.0 vs 13.4±2.1 pg/mg). Within the nicotine group, TxB₂ concentrations were lower ( P < 0.05) at the nicotine site compared to the posterior site (18.3±5.4 pg/mg). There was also a trend towards reduced 6-keto-PGF_1α in the nicotine-treated tissues compared to saline-exposed sites. These alterations in cyclooxygenase metabolites were not accompanied by changes in epithelial proliferation or histologic parameters. 12(S)-hydroxyeicosatetranoic acid (12-HETE) and leukotriene B₄ (LTB₄) were not affected by nicotine. Therefore, nicotine may not be directly responsible for the hyperplasia at habitual tobacco placement sites, but may contribute to alterations in cyclooxygenase products of arachidonic acid metabolism.     

Effect of intraventricular haemorrhage and rebleeding following subarachnoid haemorrhage on CSF eicosanoids

Summary CSF eicosanoid levels are raised following subarachnoid haemorrhage but not sufficiently to be vasoactive per se within the cerebral circulation. Rebleeding and intraventricular haemorrhage are two factors associated with a worse outcome after aneurysmal SAH. We have examined the effects of these two factors on the CSF levels of TXB₂ (TXA₂ metabolite), PG 6-keto F₁ (prostacyclin metabolite), PGF₂ and PGE₂ in 44 patients following subarachnoid haemorrhage. In 15 patients who had received no non-steroidal antiinflammatory agent or dexamethasone, intraventricular haemorrhage increased the median levels of all four eicosanoids in ventricular CSF by 2.1–5.1-fold. In 4 patients who rebled, the CSF median levels of all four eicosanoids were raised up to 250-fold over the normal range. These concentrations are just sufficient to have cerebrovascular and neuromodulatory effects.     

Facile preparation of leukotrienes C(4), D(4) and E(4) containing carbon-13 and nitrogen-15 for quantification of cysteinyl leukotrienes by mass spectrometry

With the recent ability to use combined liquid chromatography/electrospray tandem mass spectrometry to analyze for several eicosanoids in biological samples in a single and rapid experiment, heavy isotope-labeled eicosanoids are needed as internal standards in order to quantify eicosanoid analytes. The present study describes a practical preparation of cysteinyl leukotrienes (leukotriene C(4), D(4) and E(4)) with three (13)C atoms and one (15)N atom in the cysteinyl residue. The method involves solid-phase peptide synthesis to make glutathione with heavy isotopes in the cysteinyl residue and reaction of this tripeptide with commercially available leukotriene A(4) methyl ester to give labeled leukotriene C(4) methyl ester, which is hydrolyzed to labeled leukotriene C(4). Labeled leukotriene E(4) is prepared in the same way with the use of labeled cysteine. Labeled leukotriene D(4) is prepared by treatment of labeled leukotriene C(4) with commercially available γ-glutamyl transpeptidase.     

Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug–exacerbated respiratory disease

1. Download : Download high-res image (267KB)
2. Download : Download full-size image

     

Evaluation of eicosanoids in nasal lavage as biomarkers of inflammation in patients with allergic rhinitis

Introduction

Cysteinyl leukotrienes (cys-LTs), 8-isoprostane and prostaglandin E2 (PGE₂) constitute fundamental mediators in allergic inflammation; therefore we wanted to determine the utility of PGE₂, 8-isoprostane and cys-LT levels in nasal lavage as biomarkers of allergic inflammation.

Material and methods

Twenty-one patients with allergic rhinitis (AR) were included on the basis of a positive history of AR symptoms and positive results of skin prick tests to grass pollen allergens. The main exclusion criteria were: uncontrolled asthma, nasal polyps, respiratory infection, tuberculosis, neoplastic and autoimmune diseases, current smoking and immunotherapy. Both outside the pollen season and at the height of the pollen season, total nasal symptom score (TNS-4) was evaluated and the levels of cys-LTs, 8-isoprostane and PGE₂ were measured in nasal lavage fluid (NALF).

Results

Natural allergen stimulation resulted in a significant increase of TNS-4 (p < 0.001) and nasal eosinophilia (p < 0.001). The concentration of PGE₂ dominated in the NALF outside the pollen season and decreased significantly at the height of natural exposure (p < 0.01). In contrast, lower baseline concentrations of cys-LTs and 8-isoprostane increased significantly upon allergen stimulation (p < 0.05). There was a significant correlation between mean concentration of PGE₂ and eosinophil number in NALF (r = 0.67, p = 0.0439).

Conclusions

The NALF concentrations of cys-LTs and 8-isoprostane change simultaneously with TNS-4 and nasal eosinophilia. However, due to the lack of any significant correlation, their utility as markers of allergic rhinitis should be warily considered. The decrease of PGE₂ concentration in NALF which correlated with nasal eosinophilia may participate in escalation of allergic inflammation and needs further evaluation.