leukotriene-b4 and Respiration-Disorders

The leukotrienes (LTs) are 5-lipoxygenase metabolites of arachidonic acid. The synthesis and release of LTs have been demonstrated in many cells and organs, and LTs are considered to be normal products of continuous metabolism of arachidonic acid. However, although evidence in favor of a critical role for LTs in regulation of physiological functions is still scarce, a growing body of evidence suggests a role for LTs in mediation of several pathophysiological processes such as generalized or local immune reactions, inflammation, asthma, shock, and trauma. LTs have been shown to have potent actions on many essential organs and systems, including the cardiovascular system (heart, blood vessels, microcirculation), the pulmonary system (lung, airways), the central nervous system (neural, glial, and vascular elements), the gastrointestinal tract, and the immune system. In these organs the effects of LTs are mediated by specific LT receptors. Identification of LTs and characterization of their regional and systemic pathological effects, together with characterization of their receptors and elucidation of their structure-activity relationships, are fundamental to developing LT antagonists or synthesis inhibitors that might prevent or reverse LT-dependent reactions. Preliminary reports have already shown that such pharmacological agents ameliorate some aspects of disease processes in experimental animals as well as in humans. In this brief review we intend to highlight the evidence that implicates LTs in normal physiological functions as well as in disease processes.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Central Nervous System; Central Nervous System Diseases; Humans; Hypersensitivity; Inflammation; Leukotriene B4; Respiration Disorders; Respiratory Physiological Phenomena; SRS-A; Vasomotor System; Wounds and Injuries

The clinical and molecular effects of whole-body polarized light treatment on children suffering from recurrent respiratory infection were studied.. The incidence and duration of respiratory symptoms as well as the length of appropriate antibiotic therapy were measured. Simultaneously, the genome-wide gene expression pattern was examined by whole genome cDNA microarray in peripheral lymphocytes of children.. Twenty of 25 children showed a marked clinical improvement, while in five of 25 had poor response or no changes. The gene expression pattern of the patients' peripheral lymphocytes was compared in favorable and poor responders. The lymphocytes of the children with a documented improved clinical response to polarized light therapy showed a decrease in the expression of chemokine genes, such as CXCL1, CXCL2, CXCL3, and IL-8, and in that of the TNFα gene. On the contrary, a rapid elevation was found in the expression of the gene encoding for CYP4F2, a leukotriene B4-metabolizing enzyme. In children with poor clinical response to polarized light therapy, no similar changes were detected in the gene expression pattern of the lymphocytes.. The improved clinical symptoms and modified gene expression profile of lymphocytes reveals an anti-inflammatory effect of whole-body polarized light irradiation.

Topics: Anti-Inflammatory Agents; Chemokines; Child; Child, Preschool; Female; Gene Expression; Genome-Wide Association Study; Genome, Human; Humans; Infant; Inflammation; Leukotriene B4; Light; Lymphocytes; Male; Oligonucleotide Array Sequence Analysis; Recurrence; Respiration; Respiration Disorders; Respiratory Tract Infections

Leukotrienes (LTs) C4 and B4 are potent proinflammatory mediators with a wide variety of biologic activities, including smooth muscle contraction, mucus hypersecretion, and leukocyte activation, which may be of particular relevance to the pathology of asthma and other respiratory diseases. We measured the concentrations of LTC4 and LTB4 in bronchoalveolar lavage fluid from 16 atopic subjects with asthma (eight symptomatic and eight asymptomatic) and from 14 control subjects without asthma (six with hay fever and eight nonatopic). The amounts detected in symptomatic subjects with asthma were significantly higher than in control subjects (LTB4, 0.58 +/- 0.06 versus 0.36 +/- 0.05 pmol/ml, p less than 0.05; LTC4, 0.36 +/- 0.1 versus 0.12 +/- 0.02 pmol/ml, p less than 0.01). LTC4 and LTB4 were also measured in 17 patients: nine with interstitial lung disease of varying etiology (cryptogenic fibrosing alveolitis [CFA] or idiopathic pulmonary fibrosis), three with sarcoidosis, one with extrinsic allergic alveolitis, one with sulphonamide-induced pneumonia, and one patient with eosinophilic granuloma. The concentrations of LTB4 (but not LTC4) were significantly greater in patients with CFA compared with normal control subjects (0.69 +/- 0.3 versus 0.36 +/- 0.05 pmol/ml, p less than 0.01). There was a significant correlation (p less than 0.05) between the percentage of neutrophils and the concentration of LTB4 in the bronchoalveolar lavage fluid) of the group with interstitial lung disease as a whole. This study provides evidence for a role for LTs in the airways of subjects with day-to-day asthma and suggests that LTB4 may also be involved in the recruitment of granulocytes into the lung in patients with CFA.

Topics: Adult; Asthma; Bronchoalveolar Lavage Fluid; Cross-Sectional Studies; Female; Humans; Leukotriene B4; Male; Middle Aged; Respiration Disorders; SRS-A