75 research outputs found
Cytokine modulation for anti-allergic treatment
No full textIn the complex pathogenesis of airway inflammation seen in asthma, several cytokines are recognized to play a crucial role. Modulation of the effect of these cytokines can provide alternative and more specific treatment approach to currently widely-used systemic immunosuppression by glucocorticoids. Theoretically, cytokine modulation can be achieved via several pathways, including inhibition of released cytokines by using antibodies or soluble receptors, blocking cytokine receptors, inhibiting signal transduction or preventing cytokine gene transcription. Also, some cytokines are known to possess anti-inflammatory effects in allergic inflammation, being thus themselves potentially used as a therapeutic agent. The current review discusses the present knowledge on the involvement of cytokines in the pathogenesis of allergic asthma and the experience on modulation of the effect of these cytokines in clinical situations
Intervention studies in rat allergy model and in human patients with seasonal allergic rhinitis
No full textAllergic diseases are common disorders requiring active intervention. Several theoretically promising approaches for management of allergic diseases have recently evolved, but not all aspects of these interventions have been extensively studied. Furthermore, concerns about the use of the effective and common anti-allergic treatment with glucocorticoids have emerged, based on in vitro evidence and on some in vivo suggestions, that glucocorticoids can enhance production of immunoglobulin (Ig)E.The aims of this thesis were to determine the regulatory effects of glucocorticoids, IL-2 and IL-2 receptor (IL-2R) targeted treatment and the bystander suppression phenomenon on in vivo IgE production and the effect of a leukotriene receptor antagonist on clinical symptoms in human patients with seasonal allergic rhinitis. For that purpose, Brown-Norway rats (BNR) were sensitised with occupational allergen trimellitic anhydride (TMA), and randomised double-blind placebo-controlled clinical trials were performed with human patients with seasonal allergic rhinitis.Intradermal sensitisation with TMA in BNR resulted in production of IgE anti-TMA antibodies with the highest levels at 7 weeks after sensitisation with 3% of TMA. The production of IgE anti-TMA antibodies was attenuated by administration of a glucocorticoid betamethasone if given both during and after sensitisation and by cyclosporin A only if given during sensitisation. By contrast, an IL-2-toxin DAB389IL-2, which reduced the number of IL-2R bearing cells by 30%, enhanced IgE anti-TMA antibody production, but suppressed delayed-type hypersensitivity (DTH) reaction.A phenomenon of bystander suppression has been observed after inducing oral tolerance by feeding a soluble antigen and subsequent sensitisation with this antigen together with a bystander antigen. The possibility to induce bystander suppression against the hapten TMA in rats made tolerant to ovalbumin (OvA) was evaluated. OvA-tolerant rats showed a suppressed DTH, but unaffected IgE antibody production against TMA, implying bystander suppression at the Th1 level. Thus, it is possible to induce bystander suppression against the hapten TMA, but this suppression is more pronounced for the Th1-type of immune responses.In a placebo controlled study in human patients with seasonal allergic rhinitis, treatment with nasal beclomethasone (BDP), started from the beginning of the birch pollen season, inhibited the pollen induced increase in specific IgE levels by the end of the 5-week birch-pollen season, whereas the total IgE levels were not affected. Together with results from the study with rats, these findings demonstrate that in vivo administration of glucocorticoids does not increase, but on the contrary, decreases IgE antibody production.Leukotriene receptor antagonists have recently become available for asthma treatment and they have been suggested to be beneficial also in the treatment of allergic rhinitis. In a randomised placebo-controlled study, the effect of a leukotriene receptor antagonist, zafirlukast was compared to nasal BDP in allergic rhinitis patients over a grass-pollen season. Zafirlukast-treated patients had similar degree of nasal symptoms compared to the placebo group, whereas BDP-treated patients had significantly less symptoms compared to both placebo and zafirlukast groups. Also, only treatment with BDP protected against the seasonal increase in the number of local eosinophils. These results favour the use of nasal glucocorticoid over leukotriene receptor antagonist in the treatment of seasonal allergic rhinitis.In conclusion, this thesis demonstrates the beneficial role of glucocorticoids both during the sensitisation and effector phases of allergic diseases with attenuation of antigen-specific IgE production, arguing strongly against glucocorticoids upregulating IgE in vivo. The bimodal effect of IL-2 in the immune system may depend on the degree of changes in the number of IL-2R bearing cells. The presented results were unable to demonstrate the beneficial role of bystander suppression in downregulation of Th2 (allergic)-type of immune responses nor a leukotriene receptor antagonist, zafirlukast, in the treatment of seasonal allergic rhinitis
Effect of intrapleural streptokinase administration on antistreptokinase antibody level in patients with loculated pleural effusions
No full textBACKGROUND: Streptokinase is widely used IV for the treatment of myocardial infarction and intrapleurally for the treatment of loculated pleural effusions. IV administration of streptokinase is known to cause the production of antistreptokinase antibodies. OBJECTIVE: The aim of this study was to evaluate whether the intrapleural administration of streptokinase results in a similar elevation of the serum antistreptokinase antibody level. METHODS: During 1 year, venous blood samples were taken from 16 consecutive patients (10 men and 6 women; age range, 22 to 60 years) requiring intrapleural streptokinase administration (250,000 IU once a day, for 2 to 6 days). Blood samples were taken before treatment, on day 5, and day 14. Antistreptokinase antibodies were measured using enzyme-linked immunosorbent assay (ELISA) and were expressed in arbitrary ELISA units. Four patients with myocardial infarction treated with IV streptokinase (1,500,000 IU) were included as control subjects for the method. RESULTS: Before treatment, the median antistreptokinase antibody level in patients with loculated pleural effusions was 729 ELISA units (range, 196 to 13,529 ELISA units) and increased to 9,240 ELISA units (range, 1,456 to 77,389 ELISA units) by day 14 (p < 0.0001). In the control group, the median pretreatment level was 119 ELISA units, and by day 14 it had increased to 20,495 ELISA units. Four patients who developed an elevated body temperature after intrapleural administration of streptokinase had a significantly higher pretreatment antistreptokinase antibody level compared to other patients. CONCLUSIONS: The intrapleural administration of streptokinase results in the elevation of the serum antistreptokinase antibody level, which is similar to the case with IV administration. An increased pretreatment antistreptokinase antibody level does not influence the result of intrapleural fibrinolysis but can cause an elevation of body temperature after the administration of streptokinase
Fast onset of effect of budesonide/formoterol versus salmeterol/fluticasone and salbutamol in patients with chronic obstructive pulmonary disease and reversible airway obstruction
No full textBACKGROUND AND OBJECTIVES: Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction. METHODS: In this double-blind, double-dummy, crossover study, 90 patients (aged >or=40 years; FEV(1) 30-70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 microg, salmeterol/fluticasone 25/250 microg, salbutamol 100 microg or placebo (via pressurized metered-dose inhalers) on four visits. The primary end-point was change in FEV(1) 5 min after drug inhalation; secondary end-points included inspiratory capacity (IC) and perception of onset of effect. RESULTS: Budesonide/formoterol significantly improved FEV(1) at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV(1) following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV(1) improvements (P <or= 0.0001) at 180 min. Active treatments improved IC at 15 and 185 min compared with placebo (P < 0.0001). Maximal IC was greater with budesonide/formoterol than salmeterol/fluticasone (P = 0.0184) at 65 min. Patients reported a positive response to the perceptions of the onset of effect question shortly after receiving active treatments (median time to onset 5 min for active treatments vs 20 min for placebo), with no significant difference between active treatments. CONCLUSION: Budesonide/formoterol has an onset of bronchodilatory effect in patients with COPD and reversible airway obstruction that is faster than salmeterol/fluticasone and similar to salbutamol
The duration of bronchodilation of salmeterol and salbutamol as measured by specific airway conductance in healthy subjects
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