Pulmonary and Vascular Effects of Leukotrienes: Involement in Asthma and Inflation

  • Per Hedqvist
  • Sven-Erik Dahlén
Part of the NATO ASI Series book series (NSSA, volume 95)


The prostaglandins, thromboxanes and leukotrienes comprise a complex system of bioregulators, synthesized on demand in almost every tissue, and demonstrating a broad range of activities. They all derive from some closely related polyunsaturated fatty acids, particularly arachidonic acid, which may be oxidized and further transformed in reactions initiated either by a fatty acid cyclooxygenase or, alternatively by a number of lipoxygenases. Prostaglandins, prostacyclin (PGI2) and thromboxane A2 (TXA2) are formed via the cyclooxygenase pathway, whereas leukotrienes, lipoxins, and related monohydroxy acids are generated by specific lypoxygenases. Most of the products thus formed either contract of relax vascular and nonvascular smooth muscle, and several of them have been implicated a mediator role in various inflammatory and hypersensitivity reactions. The antiflogistic effect of aspirin and related non-steroidal antiinflammatory drug (NSAID:s). is well established, and apparently correlates with the capacity to inhibit the formation of cyclooxygenase products, notably PGE2, PGD2, and PGI2. Although these three substances are considered proinflammatory and potently enhance the response to other stimuli, they do not themselves elicit significant edema, and their pain producing capacity is at best moderate (cf. Kuehl and Egan, 1980; Goetzl, 1981). The same prostaglandins seem to have no effect per se on activation or migration of leukocytes, although they have been reported to enhance chemokinesis (Goetzl et al., 1979) and to inhibit the release of lysosomal enzymes induced by other stimuli (Weissman et al., 1980). In the pulmonary system, PGD2, PGF2a, and TXA2 are potent broncho-constrictors, and most asthmatic patients are remarkable hyperreactive to inhalation of PGF9 (Mathé et al., 1973; Pasarglikian et al., 1977). Moreover, ast~iatic patients provoked by inhalation of specific allergen demonstrate increased plasma levels of 15-keto-13,14-dehydro-PGF2a, major metabolite of PGF2401, and PGD2, in correlation with the severety of the asthmatic attack (Green et al., 1974). However, cyclooxygenase inhibitors do not significantly alleviate the symptoms of asthma, and sometimes they even pre-cipitate a life-threat4n•ing reaction, the so called aspirin asthma.


Arachidonic Acid Allergen Challenge Postcapillary Venule Eicosatetraenoic Acid Hamster Cheek Pouch 
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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Per Hedqvist
    • 1
  • Sven-Erik Dahlén
    • 1
  1. 1.The National Institute of Environmental Medicine and Department of PhysiologyKarolinska InstitutetStockholmSweden

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