Urinary leukotriene E4 levels during early and late asthmatic responses†

Manning, Patrick J.; Rokach, Joshua; Jl, Malo; Ethier, Diane; Cartier, André; Girard, Yves; Charleson, S.; O'Byrne, Paul M.

doi:10.1016/s0091-6749(05)80068-5

Cited by 174 publications

(80 citation statements)

References 34 publications

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“…Measurements of the urinary metabolite LTE 4 have been performed after allergen challenge in humans, and an acute increase in LTE 4 has been shown [7]. However, a clear-cut late increase in urinary LTE 4 has not yet been shown in humans [42]. In animal models, on the other hand, where acute responses of higher magnitude can be elicited, a continuous release of cys-LTs may be detected ( [43] and present results).…”

Section: Discussionmentioning

confidence: 49%

Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

Fornhem

Kumlin²,

Jm³

et al. 1995

Eur Respir J

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A Al ll le er rg ge en n--i in nd du uc ce ed d l la at te e--p ph ha as se e a ai ir rw wa ay ys s o ob bs st tr ru uc ct ti io on n i in n t th he e p pi ig g: : m me ed di ia at to or r r re el le ea as se e a an nd d e eo os si in no op ph hi il l r re ec cr ru ui it tm me en nt t ABSTRACT: The aim of this study was to develop a novel model for studies of mediator mechanisms involved in the late asthmatic reaction in the lower airways, by using the sensitized pig. The release of histamine and cysteinyl-containing leukotrienes (cys-LTs), as well as the levels of inflammatory cells in blood and bronchoalveolar lavage fluid, were determined and their relationship to plasma cortisol levels and pulmonary airways obstruction was noted. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen, and one group of animals was treated with a cortisol-synthesis inhibitor (metyrapone) by constant intravenous infusion. Ascaris suum allergen was nebulized into the lower airways and total lung resistance, blood leucocyte count and urinary levels of methylhistamine and leukotriene E 4 (LTE 4 ) were followed for 8 h, whereafter bronchoalveolar lavage was performed for analysis of leucocytes.An increase in urinary methylhistamine and LTE 4 was seen during the acute allergic reaction in both groups of pigs. Metyrapone treatment prolonged the acute release of histamine, and this was seen together with a prolonged acute bronchoconstrictor response. In metyrapone-treated pigs, a continuous release over 8 h was seen for cys-LTs, but not for histamine. A late blood eosinophilia was also seen in metyrapone-treated animals, starting 4-6 h after allergen challenge. Late cys-LT release and eosinophilia were absent in non-metyrapone-treated animals.These results suggest that allergen-induced late release of cys-LTs as well as blood eosinophilia occur simultaneously with late-phase airways obstruction in the pig, and that all these reactions are prevented by high levels of endogenous cortisol. Eur Respir J., 1995Respir J., , 8, 1100Respir J., -1109 The association between increased numbers of eosinophils in the lung and human bronchial asthma was shown by ELLIS [1] in 1908, and is today well-established. However, the exact mechanism of action of eosinophils and the relevance of the eosinophilia sometimes seen in asthma are not yet fully understood. We wanted to establish a large animal model for studies of the initiation of allergic inflammation in the airways, and the pig has been found to be suitable for such studies [2][3][4].The mast cell plays a pivotal role in the acute asthmatic response, in that it releases mediators, such as histamine and cysteinyl-containing leukotrienes (cys-LTs) [5]. Measurements of free levels of histamine and cysLTs in plasma may be difficult, due to uncontrolled release from blood leucocytes. Therefore, the relatively stable urinary end-metabolites methylhistamine [6] and leukotriene E 4 (LTE 4 ) [7], respectively, were measured in this study. The possible involvement of cys-LTs in t...

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Section: Discussionmentioning

confidence: 49%

Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

Fornhem

Kumlin²,

Jm³

et al. 1995

Eur Respir J

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“…Further, there is a good relationship between the concentrations of LTE 4 in sputum from children with cystic fibrosis and urinary LTE 4 concentrations [17]. Finally, a close correlation between early asthmatic responses and urinary LTE 4 excretion has been demonstrated in patients challenged with allergens [18]. Thus, these facts strongly suggest that in the absence of extrapulmonary inflammation increased urinary LTE 4 excretion reflects enhanced pulmonary cysteinyl leukotriene production.…”

Section: Discussionmentioning

confidence: 80%

Cigarette smoking stimulates cysteinyl leukotriene production in man

Fauler

Frölich

1997

Eur J Clin Investigation

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Abstract. Chronic cigarette smoking is an important risk factor for pulmonary and cardiovascular diseases. An increased production of cysteinyl leukotrienes has been shown in asthma and in cardiac ischaemia. The effect of cigarette smoking on cysteinyl leukotriene biosynthesis is, however, not known. Urinary leukotriene E 4 (LTE 4 ) was measured in 30 habitual smokers and in 30 nonsmokers. In a further 12 non-smokers urinary LTE 4 excretion was assessed before and after smoking six cigarettes. In addition, the effect of transdermal nicotine on urinary LTE 4 excretion was studied in seven nonsmokers. There was a close correlation (r ¼ 0 . 92, P < 0 . 0001) between urinary excretion of LTE 4 and the number of cigarettes smoked daily by habitual smokers. Smoking six cigarettes within 12 h resulted in a significant (P ¼ 0 . 0047), twofold increase in the mean individual LTE 4 excretion in non-smokers. Transdermal nicotine had no effect on LTE 4 excretion in non-smokers. In conclusion, cigarette smoke causes a dose-related increase in cysteinyl leukotriene production in habitual smokers. Some of the adverse effects of smoking may be related to an enhanced leukotriene synthesis.

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“…Before pharmacological interventions were possible, it was furthermore established that allergen-induced airway obstruction was associated with increased urinary excretion of LTE 4 , at least during the early phase [191,192]. The findings that bronchoconstriction induced by histamine [192] or methacholine [193] had no influence on urinary LTE 4 supported the idea that the leukotrienes were released as a primary and early consequence of the allergen challenge.…”

Section: Allergenmentioning

confidence: 99%