leukotriene-c4 and Chronic-Disease

Interferon gamma (IFN-gamma) is a cytokine characterized by different biologic and immunologic activities. Leukotrienes are proinflammatory mediators released both in immediate and late allergic reactions. These facts suggest that leukotrienes and IFN-gamma might cooperate in allergic inflammation. The aim of this study was to investigate the influence of IFN-gamma on leukotriene C4 (LTC4) production by peripheral blood leukocytes isolated from the patients suffering from perennial allergic rhinitis caused by allergy to mites. Eleven patients entered the study. LTC4 released from leukocytes stimulated by Dermatophagoides pteronyssinus allergen alone, and after preincubation with IL-3 was examined. The influence of preincubation of leukocytes with IFN-gamma in concentrations of 1,10 and 100 ng/ml on mentioned allergen stimulation procedures was also investigated. The concentration of LTC4 in supernatants was measured by CAST-ELISA method. The difference between concentration of LTC4 released in medium with and without IL-3 represented the effect of priming. We observed that IFN-gamma suppressed release of LTC4 only from leukocytes incubated with IL-3 in dose-dependent fashion. On the basis of these data we can postulate that IFN-gamma inhibits IL-3 dependent cell priming, but has no influence on LTC4 secretion per se.

Topics: Adult; Allergens; Animals; Chronic Disease; Dermatophagoides pteronyssinus; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin E; In Vitro Techniques; Interferon-gamma; Interleukin-3; Leukocytes; Leukotriene C4; Male; Rhinitis, Allergic, Perennial; Time Factors

To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B2, 6-keto-prostaglandin F1 alpha, and leukotriene C4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B2 and leukotriene C4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Arachidonic Acids; Bepridil; Chronic Disease; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Leukotriene C4; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Radioimmunoassay; Single-Blind Method; Thromboxane B2

The association between asthma and sinusitis has long been recognized. Numerous studies point to a complex, yet undeniable relationship between asthma and chronic sinusitis and rhinitis. There have also been extensive attempts to characterize the inflammatory mechanisms of both disorders. Increasingly, the cysteinyl leukotrienes, a potent group of inflammatory mediators, have gained attention as important contributors to the manifestation of both disorders. Leukotriene production has been shown to be upregulated in the bronchial tissue of asthmatics. Our study sought to determine if leukotriene production was increased in the sinus mucosa of asthmatics with chronic sinusitis.. Prospective study.. Nasal polyp tissue was evaluated from 27 consecutive patients undergoing elective polypectomy. The presence of asthma was determined by patient history, their medical record, and use of asthma medication. Sinus tissue was extracted during the course of endoscopic surgery. Cysteinyl leukotrienes (CysLT) were quantified by a sensitive competitive enzyme immunoassay, and the levels of CysLT were compared in the group with and without asthma.. Cysteinyl leukotrienes were detected in 23 of 27 patients. The average level of LTC4 in non-asthmatic patients was 25.6 picograms (pg)/g. The average amount of LTC4 in asthmatic patients with sinusitis was 19.2 pg/g. There was no significant difference between the two groups (P =.64).. The presence of asthma does not correlate with increased levels of leukotrienes in the sinus mucosa of patients with chronic sinusitis.

Topics: Asthma; Chronic Disease; Female; Humans; Leukotriene C4; Male; Prospective Studies; Sinusitis

The dysregulation of the immune and inflammatory systems observed in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187-induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions.. Case-control study.. A university-affiliated acute care hospital in urban Stockholm.. Fourteen severely malnourished elderly subjects with stable non-malignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-matched controls were examined.. Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed cutaneous hypersensitivity (DCH) reaction were determined.. BMI was 16. 5 +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- SE) in the malnourished group and controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production.. Protein-energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.

Topics: Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Chromatography, High Pressure Liquid; Chronic Disease; Female; Granulocytes; Humans; Hypersensitivity, Delayed; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Leukotriene B4; Leukotriene C4; Male; Orosomucoid; Protein-Energy Malnutrition; Skin; Superoxides

Changes in leukotriene C4 levels during different degrees of myocardial ischemia in humans were examined by comparing radioimmunoassay measures of leukotriene C4 plasma levels obtained during transient and prolonged myocardial ischemia. Leukotriene C4 levels in systemic arterial and coronary sinus blood were determined in patients with chronic stable angina before and after myocardial ischemia induced either by exercise (supine bicycle ergometer exercise stress testing; n = 14; age, 52 +/- 8 years) or by coronary occlusion during angioplasty (n = 14; age 53 +/- 7 years). Temporal changes of leukotriene C4 were also followed in arterial and pulmonary artery blood within 24 h after the onset of chest pain (acute phase), and 1 day, 1 week, and 1 month later in 22 patients with acute myocardial infarction (AMI) (12 patients with thrombolytic therapy, age 61 +/- 10 years; 10 patients without thrombolytic therapy, age 60 +/- 11 years). Clinical characteristics, including coronary risk factors and the severity of coronary artery disease, were not significantly different among the groups. Exercise-induced myocardial ischemia and coronary occlusion did not induce any significant leukotriene C4 changes in the chronic stable angina patients, whereas AMI patients had significantly higher plasma leukotriene C4 levels in both arterial and pulmonary artery blood in the acute phase compared with those of chronic stable angina patients (arterial blood, 471 +/- 164 pg/ml and 477 +/- 235 pg/ml vs. 275 +/- 254 pg/ml or 240 +/- 66 pg/ml, p < 0.05; pulmonary artery blood in AMI, 543 +/- 162 pg/ml vs. 234 +/- 125 pg/ml or 225 +/- 64 pg/ml, coronary sinus blood in chronic stable angina, p < 0.05). These results suggest that leukotriene C4 is involved more in prolonged myocardial ischemia than in transient myocardial ischemia, and that leukocyte function might play a significant role in the pathogenesis of patients with AMI.

Topics: Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Arteries; Chronic Disease; Coronary Vessels; Exercise Test; Female; Follow-Up Studies; Humans; Leukotriene C4; Male; Middle Aged; Myocardial Ischemia; Pulmonary Artery; Radioimmunoassay; Thrombolytic Therapy

Chronic sinusitis is a recurrent disorder commonly found in atopic individuals, yet few studies have explored the role of inflammatory mediators in sinusitis. Sinus lavage fluid from ten patients with chronic sinusitis obtained during endoscopic surgery was analyzed for total cell counts and then assayed for histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2 (PGD2). All ten patients had been unresponsive to medical treatment, including oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4 and PGD2 were found in sinus fluid and were comparable to levels seen in nasal secretions of allergic rhinitis patients following allergen challenge. In the sinus fluid, inflammatory cells were predominantly neutrophils with only low percentages of mast cells, basophils or eosinophils. On the basis of the histamine and PGD2 concentrations in sinus fluid, we conclude that mast cell/basophil activation does occur in chronic sinusitis and may contribute to the persistent inflammation present in sinusitis.

Topics: Adolescent; Adult; Aged; Basophils; Body Fluids; Cell Count; Cell Degranulation; Child; Chronic Disease; Female; Histamine; Humans; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Mast Cells; Middle Aged; Prostaglandin D2; Sinusitis; Therapeutic Irrigation