interleukin-8 and Asthma--Exercise-Induced

Exercise-induced asthma (EIA) is common in children. In our experience, the incidence of EIA in adults with asthma was 54.4% (37 of 68), and those with and without EIA similar in many ways. Anti-cholinergic drugs were effective in patients with central airway obstruction during episodes of EIA, but disodium cromoglycate protected 80% of EIA patients regardless of the site of airway obstruction. The relationship between chemical mediators and EIA remains controversial but our data show a close relationship between the production of neutrophil chemotactic factor and the severity of EIA. To investigate the mechanism of EIA, we used hyperpnea-induced bronchoconstriction in sensitized rabbits. In this model, bronchoconstriction followed inhalation of dry air regardless of temperature; there was a refractory period, and the bronchoconstriction was completely blocked by an anti-cholinergic drug. The results of studies of inhalation of hypertonic saline, hyperosomolar solutions and amiloride suggest that hyperpnea-induced bronchoconstriction is caused by degranulation of mast cells or by vagal stimulation secondary to changes in osmolarity and in sodium concentration in the airway surface, which result from water loss induced by inhalation of dry air. Vascular phenomena are probably not involved in EIA.

Topics: Adult; Animals; Asthma, Exercise-Induced; Bronchoconstriction; Cell Degranulation; Child; Disease Models, Animal; Humans; Interleukin-8; Osmolar Concentration; Rabbits

Topics: Asthma; Asthma, Exercise-Induced; Bronchial Provocation Tests; Chemotactic Factors; Histamine Release; Humans; Interleukin-8; Leukocytes; Neutrophils; Physical Exertion

Topics: Airway Obstruction; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Cold Temperature; Dehydration; Epithelium; Humans; Interleukin-8; Muscle, Smooth; Parasympathetic Nervous System

Topics: Asthma; Asthma, Exercise-Induced; Bronchi; Chemotactic Factors; Humans; Hyperventilation; Interleukin-8; Neutrophils; Physical Exertion; Sports; Vagus Nerve

Topics: Allergens; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Humans; Interleukin-8; Lung; Molecular Weight

Exercise-induced asthma is considered in terms of the stimulus, the intermediary pathway and the response. Various controversies about each of these components are discussed. The stimulus may be cooling of the airways, loss of water or neither of these, and there is evidence for and against the identity of exercise- and hyperventilation-induced asthma. The intermediary pathway seems certain to involve the release of chemical mediators, although other neurogenic mechanisms have been proposed. Since the response is far from uniform, it may well be that different pathways are involved in different subjects. The effector mechanism appears to be bronchospasm, but recent evidence has suggested that an inflammatory response may be involved in a late reaction to exercise. The variability of exercise-induced asthma may well be due to variations in intrinsic bronchial reactivity resulting from allergenic stimulation.

Topics: Asthma; Asthma, Exercise-Induced; Bicycling; Body Temperature Regulation; Bronchial Spasm; Chemotactic Factors; Humans; Humidity; Interleukin-8; Reflex, Abnormal; Respiration; Running; Swimming; Vagus Nerve

The events which lead to airway narrowing in bronchial asthma are complex. There is little doubt that mast cell-derived pharmacological agents are involved, at least in part, in the initiation of the asthmatic response. However, the inflammatory response which follows mast cell activation might have more relevance to the daily pattern of asthma than the direct effects of mediators on bronchial tissue. Although the IgE mediated release of mediators from sensitized mast cells seems to play a role in pathogenesis in some individuals for some of the time, there is now increasing awareness that mast cells are also triggered by a number of non-immunological stimuli such as exercise/cold air, infection and agents which activate the complement system. Mast cell mediators are either pre-formed within granules or generated from membrane-bound phospholipids. The pre-formed mediators include histamine, various chemotactic peptides including ECF-A and the high molecular weight neutrophil chemotactic factor (NCF), proteases, glycosidases, and the heparin proteoglycan. The membrane-derived agents include the lipoxygenase products (e.g. LTB4 and the "SRS-A" leukotrienes-LTC4/D4/E4), prostaglandins and thromboxane in addition to the PAF-ace-tether (AGEPC). The mediators are diverse both in chemical composition and modes of actions. However, many of the pathological features of bronchial asthma can be explained on the basis of their recognised actions. These can be summarised as follows. Bronchial smooth muscle constriction (histamine, LTC4, LTD4, LTE4, PGF2 alfa, PGD2 and PAF); mucosal oedema (increased permeability--histamine, LTC4, LTD4 and PAF; vasodilation--PGD2, PGE2); mucous plugging (histamine, mono-HETEs and LTC4); inflammatory cell infiltrate (NCF, ECF-A peptides, HETEs, LTB4 and PAF); desquamation of epithelium (proteases, glycosidases, together with lysosomal enzymes, and basic proteins derived from neutrophils and eosinophils). It is likely that mild, easily reversible, episodic asthma is due largely to bronchial smooth muscle contraction whereas the late sustained response is more indicative of an inflammatory response, and dependent on the infiltration of neutrophils and eosinophils as the result of mediators which recruit and activate leucocytes. Much of the evidence for this is based on the demonstration that NCF concentrations in the serum are elevated during early and late phase, antigen- and exercise-induced asthma. Moderate to severe asthma is likely t

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Asthma; Asthma, Exercise-Induced; Bronchitis; Chemotactic Factors; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Mast Cells; Platelet Activating Factor; SRS-A

Neutrophil chemotactic factor (NCF) is a slight acidic macromolecule which is released into the circulation of asthmatic individuals following antigen provocation and an exercise task. It also appears in late asthmatic reactions with a time course of appearance which precedes the second fall in FEV1. The release of NCF was inhibited by prior administration of disodium cromoglycate (DSCG) suggesting its possible mast cell origin.

Topics: Airway Obstruction; Asthma; Asthma, Exercise-Induced; Basophils; Bronchial Provocation Tests; Chemical Phenomena; Chemistry; Chemotactic Factors; Chronic Disease; Forced Expiratory Volume; Histamine Release; Humans; Inflammation; Interleukin-8

Topics: Adolescent; Age of Onset; Air Pollution; Asthma, Exercise-Induced; Athletes; Belgium; Biomarkers; Child; Environmental Exposure; Female; Humans; Interleukin-8; Male; Prevalence; Pulmonary Ventilation; Respiratory Mucosa; Risk Factors; Sports; Uric Acid; Uteroglobin

Asthma is frequently reported in endurance athletes. The aim of the present study was to assess the long-term airway inflammatory response to endurance exercise in high-level athletes with and without asthma.. In a cross-sectional design, 20 asthmatic athletes (10 swimmers and 10 cross-country skiers), 19 athletes without asthma (10 swimmers and 9 cross-country skiers), and 24 healthy nonathletes completed methacholine bronchial challenge, lung function tests, and sputum induction on two separate days. All athletes competed on a national or international level and exercised ≥10 h·wk. The nonathletes exercised ≤5 h·wk and reported no previous lung disease. Bronchial hyperresponsiveness (BHR) was defined as a methacholine provocation dose causing 20% decrease in the forced expiratory volume in 1 s of ≤8 μmol.. BHR was present in 13 asthmatic athletes (62%), 11 healthy athletes (58%), and 8 healthy nonathletes (32%), and the prevalence differed among groups (P = 0.005). Sputum inflammatory and epithelial cell counts did not differ between groups and were within the normal range. Median (25th to 75th percentiles) sputum interleukin-8 was elevated in both asthmatic (378.4 [167.0-1123.4]) and healthy (340.2 [175.5-892.4]) athletes as compared with healthy nonathletes (216.6 [129.5-314.0], P = 0.02). No correlations were found between provocation dose causing 20% decrease and sputum cell counts.. Independent of asthma diagnosis, a high occurrence of BHR and an increased sputum interleukin-8 were found in athletes as compared with nonathletes. Airway inflammation or epithelial damage was not related to BHR.

Topics: Adolescent; Adult; Asthma, Exercise-Induced; Athletes; Bronchial Hyperreactivity; Bronchial Provocation Tests; Case-Control Studies; Cross-Sectional Studies; Female; Forced Expiratory Volume; Humans; Inflammation; Interleukin-8; Male; Methacholine Chloride; Skiing; Sputum; Swimming; Young Adult

We have previously shown that p38 mitogen-activated protein kinase (MAPK) regulates, at least in part, hyperosmolarity induced interleukin (IL)-8 expression in human bronchial epithelial cells (BEC). In the previous study, hyperosmolarity also activated c-Jun-NH2-terminal kinase (JNK); however, the role of the JNK signalling pathway has not been determined. In the present study, we examined the role of the JNK signalling pathway in hyperosmolarity induced IL-8 and RANTES production by BEC using the novel inhibitor of the JNK signalling pathway CEP 11004 in order to clarify these issues.. Bronchial epithelial cells that had been pre-incubated with SB 203580, CEP 11004 or a combination of these were exposed to a hyperosmolar medium and then the p38 MAPK and JNK phosphorylation activity in these cells and IL-8 and RANTES concentrations in the culture supernatants were determined.. The results showed that: (i) hyperosmolarity induced the threonine and tyrosine phosphorylation of p38 MAPK and JNK; (ii) SB 203580, as the specific inhibitor of p38 MAPK activity, and CEP 11004 attenuated hyperosmolarity induced p38 MAPK and JNK activity, respectively; (iii) SB 203580 and CEP 11004, but not PD 98059, partially attenuated IL-8 and RANTES production; and (iv) a combination of SB 203580 and CEP 11004 attenuated IL-8 and RANTES production in an additive fashion.. These results indicate that p38 MAPK and the JNK pathway regulate hyperosmolarity induced IL-8 and RANTES production by BEC.

Topics: Analysis of Variance; Asthma, Exercise-Induced; Bronchi; Cells, Cultured; Chemokine CCL5; Epithelial Cells; Humans; Immunoenzyme Techniques; In Vitro Techniques; Interleukin-8; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Osmolar Concentration; p38 Mitogen-Activated Protein Kinases

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH(2)-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Asthma, Exercise-Induced; Beclomethasone; Body Temperature Regulation; Bronchi; Budesonide; Cells, Cultured; Chemokine CCL5; Epithelial Cells; Glucocorticoids; Humans; Interleukin-8; Water-Electrolyte Balance

The mechanism of exercise-induced asthma (EIA) is still controversial, although the role of chemical mediator is strongly suspected. In the present study, 50 asthmatic patients were observed after exercise on bicycle ergometer during dry air breathing, and changes of plasma histamine and neutrophil chemotactic factor (NCF) were measured and effect of anti-allergic drugs was examined. 31 patients developed postexertional bronchoconstriction and their % reduction of FEV1 after exercise correlated significantly with the degree of airway hyperresponsiveness to inhaled methacholine determined by Astograph. Plasma histamine levels were examined in 20 EIA positive cases and 13 EIA negative cases, but no significant changes were observed between pre- and post-histamine levels in either group. On the other hand, NCF was elevated significantly after exercise in both EIA positive and negative cases, but postexertional NCF levels were significantly higher in EIA positive than in EIA negative cases. The relationship between % increase of NCF and the % reduction of FEV1 after exercise was significant (r = 0.472, p less than 0.05). DSCG and Azelastine protected the development of EIA in 14 out on 19 cases and 7 out of 12 cases, respectively. Pretreatment with DSCG significantly reduced the increase of NCF after exercise. These results indicates that one of the chemical mediator, NCF, may play an important role in producing postexertional bronchoconstriction in asthmatic patients.

Topics: Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Female; Histamine; Histamine H1 Antagonists; Humans; Interleukin-8; Male; Middle Aged; Phthalazines

Topics: Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Humans; Interleukin-8; Lung Volume Measurements; Physical Exertion; Sympathetic Nervous System; Water Loss, Insensible

We have previously shown that there were elevations of neutrophil chemotactic activity (NCA) and increases in the percentages of neutrophil and monocyte complement rosettes after exercise-induced asthma (EIA). These observations suggested that leukocyte activation may occur after EIA, possibly as a result of the release of mast-cell-associated mediators. In the present study, we have attempted to establish whether neutrophils and monocytes are functionally altered after EIA as assessed by changes in their cytotoxic capacity. Cytotoxicity was assessed by a direct visual killing assay using opsonized (complement-coated) schistosomula of Schistosoma mansoni as target organisms. Neutrophils and mononuclear cells obtained from 8 patients after exercise-induced asthma (EIA+ve) had increased cytotoxicity for opsonized schistosomula for as long as 60 min after exercise. These changes were preceded by elevations in the concentrations of serum high molecular weight NCA (which were maximal at 10 min after exercise). In asthmatic patients who did not develop exercise-induced asthma (EIA-ve), no significant increases in neutrophil or mononuclear cell killing of schistosomula, or serum NCA concentrations, were observed. There was a highly significant correlation (p less than 0.001) between the reduction in FEV1 and the increases in neutrophil cytotoxicity. In 5 EIA+ve patients, administration of disodium cromoglycate (cromolyn) prior to the exercise task inhibited both the enhancement in neutrophil and mononuclear cell cytotoxicity, as well as the elevations in circulating NCA and the reductions in FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Cromolyn Sodium; Cytotoxicity, Immunologic; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukocytes; Phagocytosis; Schistosoma mansoni

To investigate whether exercise- and ultrasonic "fog"-induced asthma are due to the same mechanism, i.e. mediator release induced by osmotic changes, we measured the serum neutrophil chemotactic activity before and after exercise and inhalation of "fog" in 15 asthmatic subjects. To assess changes in airway caliber we measured specific airway conductance (SGaw); to assess changes in neutrophil chemotactic activity we measured the maximum distance reached by neutrophils in a filter when challenged with the subject's serum in a Boyden chamber. In 10 subjects, SGaw decreased by more than 35% and neutrophil chemotactic activity increased significantly (P less than 0.05) both after exercise and "fog", whereas in five subjects no change occurred either after exercise or "fog". We conclude that both exercise- and "fog"-induced asthma are associated with increased serum neutrophil chemotactic activity, and that both stimuli may cause asthma by osmotically triggering mediator release from mast cells.

Topics: Adolescent; Adult; Airway Resistance; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Female; Humans; Humidity; Interleukin-8; Male; Middle Aged; Neutrophils; Physical Exertion

Topics: Adolescent; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Child; Female; Forced Expiratory Volume; Humans; Interleukin-8; Male; Pulse; Swimming

Circulating concentrations of the mast cell-associated mediators, histamine and neutrophil chemotactic factor (NCF) of high molecular weight, were measured in atopic and nonatopic asthmatics after treadmill exercise. Elevations in the concentrations of both mediators accompanied the development of exercise-induced asthma (EIA). Normal individuals did not release mediators or develop bronchoconstriction after an identical exercise. The elaboration of mediators was not due to the onset of airflow obstruction, the postexercise basophilia, or the exercise task per se. A treadmill exercise undertaken while inhaling fully conditioned air inhibited EIA and NCF release; in contrast the same exercise undertaken while breathing cold, dry air elicited EIA and the production of mediators. This suggests that the stimulus for EIA and mediator release may be identical. Late-phase asthmatic reactions occur 3 to 9 hr after exercise in some asthmatics and are accompanied by the appearance of circulating NCF, as previously reported in allergen-induced late responses. In addition to the contribution of mediators to the spasmogenic reaction in EIA, mediators may contribute to bronchial inflammation by activating circulating leukocytes. There was a kinetic increase in the expression of neutrophil C3b receptors in EIA (+) asthmatics for up to 60 min after treadmill exercise. The enhancement of C3b receptors, as evidence of neutrophil activation, was preceded by release of NCF and reductions in peak expiratory flow rates. The prior administration of cromolyn inhibited EIA, NCF release, and enhancement of C3b receptors. These changes were not observed in EIA (-) asthmatics after an identical exercise task. These findings support the view that mediators are released in EIA and may play an important role in its pathogenesis.

Topics: Asthma; Asthma, Exercise-Induced; Basophils; Chemotactic Factors; Cromolyn Sodium; Female; Histamine; Histamine Release; Humans; Hypersensitivity, Immediate; Interleukin-8; Male; Time Factors

Immediate and late asthmatic reactions may occur after inhalation of specific antigens such as house dust mites or pollens. Recently, similar dual reactions have been found to occur after asthma induced by exercise. The immediate reaction to an antigen is believed to be due to the release of preformed and newly formed mediators derived primarily from mast cells via IgE antibodies. The late reaction also appears to be the result of an IgE reaction but involves inflammation in which cells play a role. The late reaction to antigen is often more severe than the immediate reaction and may be followed by a prolonged period of "nonspecific" bronchial hyperreactivity. By contrast, the late reaction to exercise is usually less severe than the immediate reaction. Both immediate and late exercise reactions are also associated with peaks of neutrophil chemotactic factor activity. Cromolyn sodium administered before challenge modifies both the immediate and the late response to antigen and exercise. Glucocorticoids block the late but not the early reaction to antigens. Their effect on the late exercise reaction is not yet known. Albuterol prevents the initial reaction to both exercise and antigen and may modify the late reaction to exercise as well.

Topics: Albuterol; Antigens; Asthma; Asthma, Exercise-Induced; Bronchial Provocation Tests; Chemotactic Factors; Cromolyn Sodium; Forced Expiratory Volume; Histamine Release; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Interleukin-8; Mast Cells; Methacholine Chloride; Methacholine Compounds; Respiratory Hypersensitivity; Skin Tests; Theophylline

Two adults and 13 children with exercise-induced asthma had both immediate and late reductions in forced expiratory volume in one second (FEV1) after treadmill exercise. The late reactions developed 4 to 10 hours after exercise and in each instance were associated with wheezing or chest tightness (or both). Increases in neutrophil chemotactic activity, measured in the 2 adults and in 11 of the children, accompanied the reductions in FEV1 in all these subjects. In contrast, four other adults with only an immediate fall in FEV1 after exercise had only an initial elevation in neutrophil chemotactic activity, with no subsequent increase for the remaining 24-hour period. The agent responsible for the neutrophil chemotactic activity released during exercise-induced late reactions appeared to be identical to that released during immediate reactions. These observations suggest that some patients with exercise-induced asthma have late reactions that, as in the case of antigen-induced bronchoconstriction, are accompanied by the release of neutrophil chemotactic activity.

Topics: Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Chemotaxis, Leukocyte; Child; Chromatography, Gel; Female; Forced Expiratory Volume; Humans; Interleukin-8; Male; Neutrophils

Elevated levels of the mast-cell-associated serum neutrophil chemotactic factor (NCF) and an increase in blood basophil counts were observed in 6 atopic asthmatics during exercise-induced asthma (EIA). These changes were not found when the same degree of airways obstruction was elicited in the same subjects by isocapnic hyperventilation (ISH) with cold air. The NCF was unlikely to be related to the basophilia alone, because asthmatics without EIA who underwent the same exercise task, produced a similar basophilia but significantly less NCF. These findings suggest that mast-cell-associated (as opposed to basophil-associated) mediators of hypersensitivity are detectable in the bloodstream during the bronchoconstriction induced by exercise, but not by ISH.

Topics: Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Basophils; Chemotactic Factors; Cold Temperature; Female; Humans; Hyperventilation; Interleukin-8; Leukocyte Count; Male; Mast Cells; Physical Exertion

Neutrophil chemotactic factor (NCF) is a slightly acidic macromolecule which is released into the circulation of asthmatic individuals following an exercise task. Its appearance was basophil-independent, accompanied the development of airflow obstruction and its release could be inhibited by administration of disodium cromoglycate. There was no elaboration of NCF after isocapnic hyperventilation with cold air, although the same asthmatics produced NCF following treadmill exercise. Finally, NCF was also released during exercise-induced late asthmatic reactions, as in antigen-induced late responses.

Topics: Asthma; Asthma, Exercise-Induced; Basophils; Chemotactic Factors; Humans; Hyperventilation; Interleukin-8; Respiratory Function Tests

Topics: Asthma; Asthma, Exercise-Induced; Bronchial Provocation Tests; Chemotactic Factors; Cromolyn Sodium; Forced Expiratory Volume; Histamine; Humans; Interleukin-8

Topics: Anaphylaxis; Animals; Asthma, Exercise-Induced; Chemotactic Factors; Forced Expiratory Volume; Guinea Pigs; Histamine Release; Humans; Hyperventilation; Interleukin-8; Mast Cells; Molecular Weight

Significant increase in the maximum post-exercise values of plasma histamine (PH), whole blood histamine (WBH) and neutrophil chemotactic factor (NCF) occurred in arterial blood within the first hour after exercise in asthmatic patients. However, similar changes in PH and WBH also occurred in the control group. Significant increases in circulating basophil counts following exercise were found in both groups, which closely mirrored the changes in PH and NCF, and there was a highly significant correlation between rises in WBH and basophil counts (P less than 0.001). When plasma histamine as assayed in venous blood using a more sensitive and specific double isotope radio enzymatic assay no significant alteration in plasma histamine levels was detected in either the asthmatic or the control group. We conclude that there is no evidence from these studies to support the suggestion that mast cell mediator release is involved in the pathogenesis of exercise-induced asthma, and that any observed changes in levels of PH and NCF after exercise may be related to changes in levels of circulating basophils.

Topics: Adult; Asthma; Asthma, Exercise-Induced; Basophils; Chemotactic Factors; Forced Expiratory Volume; Histamine; Humans; Interleukin-8; Leukocyte Count; Male; Peak Expiratory Flow Rate; Respiratory Function Tests