Effect of long-term, low-dose clarithromycin on T helper 2 cytokines, eosinophilic cationic protein and the 'regulated on activation, normal T cell expressed and secreted' chemokine in the nasal secretions of patients with nasal polyposis.

BACKGROUND: Little is known about the effects of macrolides on the cytokines and chemokines that modulate the function of eosinophils in nasal polyposis. METHODS: Twenty-two non-allergic and 18 allergic patients with nasal polyps were administered clarithromycin 500 mg/day (single oral dose) for eight weeks. We measured the nasal secretion levels of the T helper 2 (also known as Th2) cytokines interleukin 4, 5 and 6, the 'regulated on activation, normal T cell expressed and secreted' (also known as RANTES) chemokine, and the eosinophilic cationic protein, before and after treatment. RESULTS: After clarithromycin treatment, we found reduced levels of the 'regulated on activation, normal T cell expressed and secreted' chemokine in samples from both non-allergic and allergic patients (p < 0.05). Clarithromycin treatment decreased the levels of eosinophilic cationic protein only in non-allergic patients (p < 0.05), and decreased the level of interleukin 6 only in allergic patients (p < 0.05). Decreased levels of the 'regulated on activation, normal T cell expressed and secreted' chemokine were associated with a reduction in polyp size both in non-allergic and allergic patients. CONCLUSION: Clarithromycin has a strong anti-inflammatory effect in nasal polyposis, but has different immunomodulatory effects in allergic and non-allergic nasal polyposis patients.

The effects of PG102, a water-soluble extract from Actinidia arguta, on serum total IgE levels: a double-blind, randomized, placebo-controlled exploratory clinical study.

BACKGROUND: Recent studies have reported that blocking IgE has a potentially beneficial role in the treatment of various allergic diseases. Previously, we found that PG102, a water-soluble extract prepared from the edible fruits of Actinidia arguta, can effectively reduce IgE levels using murine models. AIMS: To evaluate the efficacy of PG102 at lowering levels of total IgE in asymptomatic subjects with atopy. METHODS: A total of 90 asymptomatic subjects with atopy were randomized equally to a PG102 group or a placebo control group and treated for 8 weeks in a double-blind manner. Total serum IgE, eosinophilic cation protein (ECP), eotaxin, thymus, and activation-regulated chemokine (TARC), IL-4, IL-5, and IL-13 levels were measured. Eosinophil counts were determined before and after treatment, and results were compared. In addition, possible adverse reactions were thoroughly checked in this first human trial. RESULTS: Levels of total IgE significantly increased in the control group but showed no change in the PG102 group, and change differences between the control and PG102 groups were significant (+12.9%, vs.-5.7%, p = 0.015). Levels of ECP and eotaxin and eosinophil counts produced similar results. However, the other variables showed no significant changes after treatment. CONCLUSION: In this exploratory clinical trial, it was found that 8 weeks of treatment with PG102 effectively reduced the levels of total IgE in apparently asymptomatic subjects with atopy.

Cysteinyl leukotrienes acting via granule membrane-expressed receptors elicit secretion from within cell-free human eosinophil granules.

BACKGROUND: Cysteinyl leukotrienes (cysLTs) are recognized to act via receptors (cysLTRs) expressed on cell surface plasma membranes. Agents that block cysLT(1) receptor (cysLT(1)R) are therapeutics for allergic disorders. Eosinophils contain multiple preformed proteins stored within their intracellular granules. Cell-free eosinophil granules are present extracellularly as intact membrane-bound organelles in sites associated with eosinophil infiltration, including asthma, rhinitis, and urticaria, but have unknown functional capabilities. OBJECTIVE: We evaluated the expression of cysLTRs on eosinophil granule membranes and their functional roles in eliciting protein secretion from within eosinophil granules. METHODS: We studied secretory responses of human eosinophil granules isolated by subcellular fractionation. Granules were stimulated with cysLTs, and eosinophil cationic protein and cytokines were measured in the supernatants. Receptor expression on granule membranes and eosinophils was evaluated by flow cytometry and Western blot. RESULTS: We report that receptors for cysLTs, cysLT(1)R, cysLT(2) receptor, and the purinergic P2Y12 receptor, are expressed on eosinophil granule membranes. Leukotriene (LT) C(4) and extracellularly generated LTD(4) and LTE(4) stimulated isolated eosinophil granules to secrete eosinophil cationic protein. MRS 2395, a P2Y12 receptor antagonist, inhibited cysLT-induced eosinophil cationic protein release. Montelukast, likely not solely as an inhibitor of cysLT(1)R, inhibited eosinophil cationic protein release elicited by LTC(4) and LTD(4) as well as by LTE(4). CONCLUSION: These studies identify previously unrecognized sites of localization, the membranes of intracellular eosinophil granule organelles, and function for cysLT-responsive receptors that mediate cysteinyl leukotriene-stimulated secretion from within eosinophil granules, including those present extracellularly.

Assessment of Schistosoma mansoni induced intestinal inflammation by means of eosinophil cationic protein, eosinophil protein X and myeloperoxidase before and after treatment with praziquantel.

Faecal concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO) were measured in extracts of stool samples obtained from a cohort of people (n=182) living in Bugoigo, a fishing community on the Eastern shore of Lake Albert, Buliisa District, in North Western Uganda where Schistosoma mansoni is endemic. Samples were collected before treatment and 5, 15, 20 and 52 weeks after treatment with praziquantel. Significantly increased levels of faecal ECP and EPX were found in S. mansoni infected individuals (n=155) compared to the levels found in stools from non-infected (n=27) (median values ECP: 11.3 microg/g vs. 5.9 microg/g, P=0.005, and EPX: 413.5 ng/g vs. 232.2 ng/g, P=0.045). An increased level of MPO was also found among the infected individuals compared to the non-infected 11.6 mu/g vs. 5.3 mu/g, P=0.07). Significant but weak correlations were found between faecal egg counts and faecal concentrations of ECP and EPX. Treatment with praziquantel induced a significant decline in both ECP and EPX, but only a non-significant reduction in faecal MPO. Following reinfection and despite of very low infection intensities, the protein levels increased significantly reaching the pre-treatment level (ECP and EPX) or levels significantly higher than the pre-treatment levels (MPO). This response pattern may imply a rebound effect during reinfection following treatment and resolution of immune regulatory immunosuppressive mechanisms in function during the chronic infection.

Usefulness of sparfloxacin against Chlamydia pneumoniae infection in patients with bronchial asthma.

The efficacy of sparfloxacin (SPFX) for the control of bronchial asthma was evaluated in 26 patients with suspected Chlamydia pneumoniae infection. Patients were randomly allocated to receive SPFX 200 mg/day (n = 14) or control treatment (n = 12) for 21 days. Significant improvements in serum C-reactive protein levels, and significant decreases in peripheral eosinophil counts, serum eosinophil cationic protein (ECP) and sputum ECP were observed in the SPFX-treated group at day 21. SPFX-treated patients also had a significantly reduced frequency of asthma symptoms, reduced inhalant beta2-stimulant use, and significant increases in morning peak expiratory flow. At the end of the study, C. pneumoniae was undetectable in two SPFX-treated patients who underwent polymerase chain reaction testing, but one control patient who was tested still had detectable levels of C. pneumoniae. These results suggest that SPFX could be used to control bronchial asthma in patients with suspected persistent C. pneumoniae infection.

Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.

BACKGROUND: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery. OBJECTIVES: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol. METHODS: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes). RESULTS: There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone. CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants.

Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor-alpha (TNF-alpha), alpha1-antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cow's milk allergy (CMA) received in a randomized double-blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double-blind placebo-controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4-wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p=0.064; MIX vs. placebo, p=0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE-associated CMA infants, faecal IgA was higher for LGG than for placebo (p=0.014), and TNF-alpha was lower for LGG than for placebo, but non-significantly (p=0.111). In conclusion, 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA.

Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics.

OBJECTIVES: Inhaled corticosteroids, leukotriene receptor antagonists, and theophylline are recommended for the treatment of mild persistent asthma. The aim of this study was to compare the changes in sputum total cell and eosinophil counts, and eosinophil cationic protein (ECP) levels in serum and sputum following treatment with leukotriene receptor antagonists, inhaled corticosteroids, and theophylline in patients with mild persistent asthma. METHODOLOGY: Total cell counts, eosinophil percentage, and ECP levels in induced sputum and serum were determined both before and after treatment. Prior to sputum induction, FEV1 and PEF values and symptom scores were recorded at baseline and after 8 weeks of treatment. After baseline measurements, the asthmatic patients (n = 30) were randomized into three groups. A total of 10 patients were treated with zafirlukast, 20 mg bd, 10 with budesonide inhaler 200 microg bd, and 10 with theophylline 200 mg bd. RESULTS: There were significant decreases in sputum total cell counts and eosinophil percentage in all treatment groups. However, the decrease in sputum eosinophil counts was more significant in the corticosteroid-treated group. Although sputum ECP levels decreased significantly in the groups treated with zafirlukast and budesonide (zafirlukast group, 580-135 microg/L, P < 0.01; budesonide group, 683-268 microg/L, P < 0.01), the decrease was not statistically significant in the theophylline-treated group (498-361 microg/L, P > 0.05). In contrast, there were no significant changes in serum ECP levels in any of the treatment groups. CONCLUSIONS: All three treatments resulted in significant decreases in sputum total cell counts and eosinophil percentage, but the decrease in sputum ECP level was only seen in the groups treated with budesonide and zafirlukast. These results suggest that although all three treatments are considered as first-line treatments in most consensuses, theophylline seems to have less of an inhibitory effect on eosinophil activation.

Treatment of chronic cough in children with montelukast,a leukotriene receptor antagonist.

Twenty-two children (13 boys and 9 girls) with chronic cough were treated with the leukotriene receptor antagonist montelukast (Singulair tbl. 5 mg) administered once daily for four weeks. In 14 children (68%), the cough ceased during the third week of treatment. Children responding to montelukast were found to have higher blood levels of eosinophil cationic protein (S-ECP) in the pretreatment blood sample than children with no response (responders 14.88+/-2.651 microg/l versus nonresponders 6.62+/-0.948 microg/l; p<0.01). Blood S-ECP levels remained higher also in the post-treatment blood sample in responders (10.55+/-1.631 microg/l) compared to nonresponders (6.13+/-0.937 microg/l; p<0.05). The difference is statistically significant. There were also differences in absolute eosinophil blood count and IgE blood levels between the two groups in the pretreatment blood sample. Using 24-hour pH-metry, two children not responding to therapy were subsequently diagnosed to have gastroesophageal reflux. Judging from the results, one might deduct that patients with chronic cough who have increased levels of serum ECP and absolute eosinophil blood counts are likely to benefit from treatment with montelukast.