Differences and similarities between allergic and nonallergic rhinitis in a large sample of adult patients with rhinitis symptoms.

BACKGROUND: Allergic rhinitis (AR) and nonallergic rhinitis (NAR) may present with different clinical and laboratory characteristics. METHODS: A total of 1,511 consecutive patients, aged 18-81 years, diagnosed with rhinitis, 56% females and 44% males, underwent complete allergic evaluation including skin prick test, blood eosinophil counts, nasal eosinophil counts, peak nasal inspiratory flow (PNIF) measurement and evaluation of nasal symptoms using a visual analog scale (VAS). RESULTS: A total of 1,107 patients (73%)had AR, whereas 404 (27%) had NAR. Patients with NAR were older and predominantly female. A higher nasal eosinophils count was associated with AR and a lack of clinical response to antihistamines. AR patients had more sneezing and nasal pruritus, whereas NAR was characterized mainly by nasal obstruction and rhinorrhea. AR patients had more severe symptoms and recurrent conjunctivitis, whereas NAR patients had slightly more frequent episodes of recurring headaches as well as olfactory dysfunction. PNIF, blood eosinophil counts and VAS of nasal symptoms were higher in patients with AR. In a final logistic regression model, 10 variables were statistically different between AR and NAR: age [OR 0.97 (95% CI 0.96-0.98)], sneezing [OR 4.09 (95% CI 2.78-6.00)], nasal pruritus [OR 3.84 (95% CI 2.60-5.67)], mild symptoms [OR 0.21 (95% CI 0.09-0.49)], intermittent/severe nasal symptoms [OR 3.66 (95% CI 2.06-6.50)], VAS [OR 1.06 (95% CI 1.04-1.08)], clinical response to antihistamines [OR 22.59 (95% CI 13.79-37.00)], conjunctivitis [OR 4.49 (95% CI 2.86-7.05)], PNIF [OR 1.01 (95% CI 1.00-1.01)] and nasal eosinophil counts [OR 1.14 (95% CI 1.10-1.18)]. Receiver operating characteristic analysis showed high predictive accuracy for a model including these variables independently of the diagnosis of AR/NAR (cutoff <0.74). CONCLUSIONS: We showed that the several clinical and laboratory parameters reported above may help to reinforce or exclude the diagnosis of AR obtained with skin prick test.

Polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein are associated with chronic spontaneous urticaria and urinary leukotriene E4.

The mechanisms of chronic spontaneous urticaria (CSU) continue to be unknown. Our working hypothesis is that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be involved in the pathways leading to CSU. We examined five candidate polymorphisms of cyclo-oxygenases 1 and 2 and of 5-lipo-oxygenase-activating protein in 109 controls and in 94 CSU patients from Northern Italy. We also examined the levels of urinary leukotriene E4 (LTE4) before and after challenge with ASA. A multiple regression model was found to show that COX-2 5'UTR T/G, COX-2 Exon 10 T/C, and FLAP -336 G/A polymorphisms were significantly associated with CSU, with the minor allele more represented in CSU group. Similar results were obtained as regards the specific association with ASA-tolerated CSU and ASA-exacerbated CSU. Evaluating a polygenic model, reflecting the sum of the concomitant alleles associated with CSU (i.e. COX-2 5'UTR G allele, COX-2 Exon 10 C allele, and FLAP -336 G/A allele), the proportion of CSU patients increased progressively with the increasing number of unfavourable alleles. Finally, in a linear regression model after adjustment for disease status COX-1 22 T carriership remained a significant predictor of post-challenge high urinary LTE4 levels. Our results support the hypothesis that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be associated with CSU.

Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.

BACKGROUND: To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. OBJECTIVE: We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. METHODS: We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. RESULTS: The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. CONCLUSION: The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica, Olea europea, and house dust mite.

Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is considered to be an autoimmune disease of unknown aetiology that affects the mucosae, especially the oral cavity. OBJECTIVE: We compared tacrolimus 0.1% ointment and clobetasol 0.05% ointment for the treatment of OLP. PATIENTS AND METHODS: A total of 32 patients (20 females and 12 males; all white, Italian origin, mean age of 43.6+/-18.4 years; 16 patients per treatment group) were treated with tacrolimus or clobetasol ointment for 4 weeks in a randomized, double-blind, clinical trial. Pain severity, burning sensation, and mucosal lesion extension were assessed using a four-point scale. RESULTS: At the end of the treatment period, symptom scores were significantly lower in the tacrolimus group than in the clobetasol group. CONCLUSION: The results of this study suggest that tacrolimus 0.1% ointment is more effective than clobetasol propionate 0.05% ointment in the treatment of OLP. However, other studies are needed to confirm the effectiveness of this treatment before it can be recommended for use in clinical practice.

Comparison of topical tacrolimus 0.1 % in pectin ointment with clobetasol 0.5% ointment in adults with moderate to severe desquamative gingivitis: A 4-week, randomized, double-blind clinical trial.

BACKGROUND: Desquamative gingivitis (DG) is a clinical condition characterized by red, painful, glazed, and friable gingiva, which might be a manifestation of some autoimmune mucocutaneous diseases. The time from the development of initial signs of DG to diagnosis can vary from months to years. Based on a literature search, no data concerning patients with DG without signs of autoimmune disease were available. OBJECTIVE: The aim of this trial was to compare the efficacy and tolerability of monotherapy with topical tacrolimus 0.1% in pectin ointment versus clobetasol propionate 0.5% ointment in adults affected by DG. METHODS: This randomized, double-blind clinical trial was conducted at the Dipartimento di Medicina Clinica e Sperimentale, Universita di Verona, Verona, Italy. Patients aged > or =18 years were selected using the department's electronic medical records based on a clinical diagnosis of moderate to severe DG. After a 2-week washout period, patients were randomly assigned to receive 2 mL of tacrolimus 0.1% in pectin (equivalent to 0.2 mg of tacrolimus) or 2 mL of clobetasol propionate 0.5% ointment (equivalent to 1 mg of clobetasol) QD for 4 weeks. Evaluations were performed before treatment (baseline), after the treatment period (week 4), and at 2 follow-up visits at weeks 6 and 8. The signs of DG (ie, erythema [atrophy] and desquamation [erosions/ulceration]) were quantified by a blinded investigator using a calculated score based on their surface extension, using a drawing in which the areas of various zones of the mouth were indicated as a percentage of the whole oral mucosa. Severity of erythema and desquamation was rated on a 4-point scale (0 = absent; 1 = involvement of <5% of surface [mild]; 2 = 5%-15% [moderate]; and 3 = >15% [severe]). The primary end point was the number of patients who achieved remission (severity score of 0) in either sign; the secondary end point was the proportions of patients achieving improvement (severity score of 0 or 1) in either sign. Before and after treatment, we measured the serum concentrations of tacrolimus and its metabolites with an immunoenzymatic assay kit. Tolerability was assessed using hematology, biochemistry, urinalysis, measurements of systolic/diastolic blood pressure and heart rate, patient interview, and spontaneous reporting. RESULTS: A total of 24 patients (18 women, 6 men; all white of Italian origin; age range, 21-65 years; 12 patients per treatment group) were enrolled in the study. In the tacrolimus group, 11 (91.7%) patients achieved remission of erythema and/or desquamation at weeks 4 and 6; at week 8, these rates were 9 (75.0%) and 8 (66.7%), respectively; none of the patients in the clobetasol group achieved remission of either sign at any time point (all, P < 0.001). At weeks 4, 6, and 8, significantly greater proportions of patients treated with tacrolimus had improved erythema and desquamation compared with those treated with clobetasol (all, P < 0.001). At week 4, all patients had undetectable serum tacrolimus concentrations (<1.5 microg/L). Six (50.0%) patients in the tacrolimus group reported a mild oral burning sensation, and 6 (50.0%) patients in the clobetasol group reported mild mouth dryness. No other adverse events were reported. CONCLUSIONS: The results of this small study suggest that topical tacrolimus 0.1 % in pectin was more effective compared with clobetasol propionate 0.5% ointment in the treatment of DG. Both treatments were generally well tolerated in the population studied.

Food allergy in gastroenterologic diseases: Review of literature.

Food allergy is a common and increasing problem worldwide. The newly-found knowledge might provide novel experimental strategies, especially for laboratory diagnosis. Approximately 20% of the population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the "gold standard" for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be classified on the basis of immunologic or nonimmunologic mechanisms and the organ system or systems affected. Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges. The primary therapy for food allergy is to avoid the responsible food. Antihistamines might partially relieve oral allergy syndrome and IgE-mediated skin symptoms, but they do not block systemic reactions. Systemic corticosteroids are generally effective in treating chronic IgE-mediated disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental therapies for IgE-mediated food allergy have been evaluated, such as humanized IgG anti-IgE antibodies and allergen specific immunotherapy.

Relationship between human leucocyte antigen class I and class II and chronic idiopathic urticaria associated with aspirin and/or NSAIDs hypersensitivity.

BACKGROUND: HLA genes play a role in the predisposition of several diseases. The aim was to analyze the prevalence of HLA class I phenotypes and HLA-DRB1* genotype in patients with CIU associated with ASA and NSAIDs hypersensitivity (AICU). METHODS: 69 patients with AICU, and 200 healthy subjects. RESULTS: Subjects with HLA-B44 and HLA-Cw5 antigens were more represented in patients with AICU than in control group. Subjects with HLA-A11, HLA-B13, HLACw4, and HLA-Cw7 antigen were more represented in control group than in patients with AICU. Multiple logistic regression demonstrated an association of HLA-Cw4 and HLA-Cw7 with a lower risk of AICU, whereas carriers of HLA-B44 phenotype had a higher risk of AICU. No differences were found between patients and controls as regards to HLA-DRB1* genotype. CONCLUSIONS: We observed an association between some HLA class-I antigens and AICU. To the best of our knowledge this is the first description of such association.

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.

BACKGROUND: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. METHODS: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. RESULTS: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. CONCLUSIONS: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.

Circulating levels of soluble adhesion molecules in patients with ANCA-associated vasculitis.

BACKGROUND: During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules, which facilitate the binding of circulating leukocytes and their extravasation in surrounding tissue (i.e. renal tissue). The serum concentration of circulating soluble adhesion molecules is supposed to reflect the degree of this activation. OBJECTIVE: In the first part of the study, we determined if the serum levels of the soluble intercellular adhesion molecule (sICAM)-1 and the soluble endothelial cell-leukocyte adhesion molecule (sELAM)-1, in patients affected by microscopic polyangiitis (MPA), associated with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA), were related to the active and the inactive vasculitis phase. In the second part of the study, we examined the changes in circulating sICAM-1 and sELAM-1 levels and the clinical outcome of renal function in these patients. METHODS: We examined 20 MPO-ANCA-positive MPA patients in an acute phase and in a remission phase, after 6 months of treatment, and 50 subjects as controls, 30 with autosomal dominant polycystic kidney disease (ADPKD) in stable chronic renal failure (CRF) and 20 healthy volunteers (HS) with normal renal function. RESULTS: Regarding serum creatinine (Cr) concentration, no significant differences were found comparing active and inactive phases in the MPA group and the CRF group. Mean serum adhesion molecule levels in the MPA group were higher in the active phase compared to the inactive phase and to the CRF and HS groups. In addition, considering the outcome of serum Cr concentrations in the MPA group, the serum adhesion molecule levels were higher and decreased more slowly in patients with final high serum Cr concentrations than in patients with final normal serum Cr concentrations. CONCLUSION: Our data suggest that in MPO-ANCA-positive MPA patients, higher sICAM-1 and sELAM-1 levels during the active phase and their slower decline during the treatment period, could be a prognostic risk factor for CRF development.

Randomized placebo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria.

BACKGROUND: H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus, and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria (CIU). Recently, antileukotriene receptors have been used in patients with CIU, either administered as monotherapy or combined with H 1 -receptor antagonists. OBJECTIVE: We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist, 10 mg of montelukast daily, and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo. METHODS: One hundred sixty patients aged 18 to 69 years (mean +/- SD, 43.9 +/- 13.4 years) with a history of moderate CIU were selected. A randomized, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Patients were treated with 5 mg of desloratadine once daily (n = 40), 10 mg of montelukast once daily (n = 40), 5 mg of desloratadine (n = 40) in the morning plus montelukast in the evening, or matched placebo (n = 40). Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously. RESULTS: Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study. Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment. As reflective evaluation, all groups showed significant differences compared with the placebo group in terms of total symptom score, number of hives, and size of largest hive. In addition to the pruritus, only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo, whereas there were no differences between the montelukast and placebo groups. Finally, no differences were found between the desloratadine group and the desloratadine plus montelukast group. The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group, whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive. No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group. CONCLUSIONS: The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU. In addition, the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU.

Serum levels of soluble CD30 in adult patients affected by atopic dermatitis and its relation to age, duration of disease and Scoring Atopic Dermatitis index.

The value of CD30 and the soluble circulating fragment of CD30 (sCD30) for atopic dermatitis (AD) remains unclear. In particular, little is known about the effects of age, duration of disease and Scoring Atopic Dermatitis index (SCORAD) on the levels of serum sCD30 in patients affected by AD. In the present study, we have analysed serum sCD30 levels of adult patients affected by AD. The study's population includes 18 non-smoking outpatients, with a diagnosis of AD. As a control group we studied 18 non-atopic subjects from laboratory staff, matched for sex and age. These subjects had no history of AD, urticaria or seasonal or perennial rhinitis or asthma, and had negative skin prick test to a panel of allergens. The sCD30 serum levels were clearly higher in patients affected by AD (14.2+/-9.0 IU/ml) than in healthy subjects (1.2+/-0.8 IU/ml) (p<0.001). No differences were observed between males and females affected by atopic dermatitis, regarding age, duration of disease and SCORAD. Significant correlations were found between serum levels of sCD30 levels and age (r=-0.55; 95% confidence interval (CI) for r (Fisher's z transformed)=-0.81 to -0.12; p=0.01), duration of the disease (months) (r=-0.64; 95% CI for r (Fisher's z transformed)=-0.85 to -0.24; p=0.004) and SCORAD (r=-0.74; 95% CI for r (Fisher's z transformed)=-0.89 to -0.42; p=0.004). As demonstrated by the close correlation with age, duration of disease and SCORAD, serum levels of sCD30 appear to be an additional marker for the follow-up of AD.

A study of age-related IgE pathophysiological changes.

The literature on immunosenescence has focused mainly on T cell impairment. However, it is well known that B function is also profoundly affected. In particular, several studies have shown age-related changes in immunoglobulin serum levels. Concerning allergic diseases, the incidence of onset of allergic symptoms, as well as their severity, seems to decrease with age. So, the decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total IgE due to an unbalance of cytokines and soluble factors involved in its production. To gain insight into the mechanisms of age related incidence of onset of allergic symptoms, as well as their severity, in this study we have evaluated in a sample of young (12 females and 15 males, range 20-64 years) and old (42 females and 20, males range 70-93 years) individuals serum values of IgE and sCD23 and in vitro Type 2 cytokine production. Total serum IgE levels were quantified by CAP-system fluorescence enzyme immunoassay. Serum CD23 levels were measured by a sandwich enzyme-linked immunoassay. Enzyme immunoassay tests have been used to quantify IL-4, IL-10 and IL-13 on mitogen-stimulated cultures. Serum total IgE and sCD23 in the two groups of young and old subjects were not significantly different. No detectable levels of IL-4, IL-10 and IL-13 were observed in supernatants from unstimulated cultures in all the subjects tested. After 48 h stimulation with PHA, cytokine amounts became detectable in all subjects. However, the values of the cytokines under study were not significantly different between young and old subjects. In our study, we have not been able to show no impairment in the afferent (type 2 cytokine production) and in the central (serum IgE and sCD23 levels) branch of allergic responses. Previous studies have shown that the efferent branch, at least studied as basophil releasability and bronchial responsiveness, is not impaired in elderly. In conclusion, as suggested from the present and previous papers it is questionable whether there is sufficient information to validate the statement that the incidence of allergic diseases decreases with age.

[Neutrophils in rheumatoid inflammation]. / Il neutrofilo nella flogosi reumatoide.

For many years a secondary role in the pathogenesis of rheumatoid arthritis has been ascribed to neutrophil, relatively to the inflammatory response's evaluation. This cell was considered lacking in a peculiar activity and ever depending on lymphocytes and monocytes. During the recent years the neutrophil has been recognized as a cytokines producing cell, really able to modulate its role in joints inflammation. In the light of the latest information it's possible reconsider the role of this cell, looking at it like a moderate co-protagonist in the expression of rheumatoid damage, regarding both to joint inflammation and the maintenance of the damage itself. On the grounds of these knowledge, polymorphonuclear granulocyte could be also chosen as target of the newest therapies in the treatment of this disease. The aim of this short review is to focus the activity of neutrophils in rheumatoid arthritis, trying to follow them through their migration from blood to sinovial tissue and to understand the dynamic relation with the cytokine network, that from these cells pathway depends.

Prevalence of latex sensitization in health care workers of a general hospital in Palermo, Sicily.

STUDY OBJECTIVE: To assess the prevalence of latex sensitization in a group of hospital employees in a general hospital. DESIGN: Cross-sectional study on hypersensitivity to latex gloves among health-care workers. SETTING: A general hospital in Palermo, Sicily. PATIENTS: 196 health-care workers answered a questionnaire about their case history of allergic diseases (i. e., rhinitis and/or asthma) and about symptoms after wearing latex gloves. All subjects were tested by skin prick test (SPT) with commercial latex extract and aeroallergens and had blood draw for total serum IgE and latex-specific IgE testing and glove-use test. MAIN RESULTS: 42% of the subjects who answered the questionnaire reported at least one symptom after wearing latex gloves. All symptoms were local, and none of the subjects reported systemic reactions. The most common symptom was itching, but none of subjects with only itching presented a positive SPT or specific serum IgE to latex. The SPT to latex was positive in 19 of 196 subjects (9.7%). Specific IgE to latex were found in 15/196 subjects (7.6%). Glove-use test was positive in 14/196 (7.1%). CONCLUSIONS: The overall prevalence of latex sensitivity in health-care workers in our epidemiological setting is 7.1%. An accurate diagnosis must take in account the integration of in vivo and in vitro tests with previous history of allergic disease.

The T cell receptor repertoire in psoriatic synovitis is restricted and T lymphocytes expressing the same TCR are present in joint and skin lesions.

OBJECTIVE: To investigate the T cell receptor (TCR) repertoire in psoriatic synovitis and to determine whether T lymphocytes in joint and skin lesions show the same Vbeta CDR3 region. METHODS: The expression of Valpha and Vbeta families was evaluated by reverse transcriptase-polymerase chain reaction. The CDR3 region of some Vbeta families was analyzed by cloning and sequencing. RESULTS: We found a diverse variable beta chain usage within psoriatic synovial fluid of 11 patients although some Valpha and Vbeta families were more frequently expressed without evidence of clonality. Analysis of TCR in skin and synovial lesions of 3 patients showed identical CDR3 sequences, indicating that T cells bearing the same TCR are present at the 2 sites of chronic inflammation. CONCLUSION: These data suggest that common or similar crossreactive antigens present in the 2 locations are responsible for the expansion of the same TCR-bearing T cells possibly already activated by a superantigen. This supports the hypothesis that both polyclonal and oligoclonal lymphocyte activation contribute to the initiation and persistence of psoriatic arthritis.

In vitro effects of fluticasone propionate on IL-13 production by mitogen-stimulated lymphocytes.

BACKGROUND: Corticosteroid administration produces multiple immunomodulatory effects, including down-regulation of cytokine production by CD4 T lymphocytes. Fluticasone propionate (FP) (Glaxo Smith&Kline, Greenford, UK), a highly lipophilic topical corticosteroid, has been shown to be safe and effective in the treatment of asthma and of both seasonal and perennial rhinitis. AIMS: To gain insight into the mechanisms of FP therapeutic effects, we evaluated interleukin (IL)-13 (a type 2 cytokine that seemingly plays a pivotal role in allergic mechanisms) production by mitogen-stimulated peripheral blood mononuclear cells (MNC) in vitro, treated or not with FP. METHODS: MNC from 10 healthy subjects and 10 asthmatic atopic patients with Parietaria allergy were stimulated v/v with phytohaemagglutinin (PHA) (50 gamma/ml) or with complete medium alone as a control. Culture supernatants, in vitro treated or not with 10(-7) or 10(-8) M FP, were collected after 48 or 72 h incubation. IL-13 production was assessed by enzyme-linked immunosorbent assay. In random selected samples, after 4 or 24 h of cell cultures, RNA was extracted and IL-4 and IL-5 reverse transcriptase-polymerase chain reaction (RT-PCR) products analyzed. RESULTS: At 48 h, there were no differences in IL-13 concentration in PHA-stimulated cultures between healthy subjects and asthmatic patients (93.6 +/- 18.9 versus 111.0 +/- 25.1 pg/ml). At 72 h, similar results were obtained (63.9 +/- 3.0 versus 73.3 +/- 2.5 pg/ml, respectively). At this time, however, IL-13 concentrations were significantly decreased versus 48 h both in asthmatics (p < 0.001) and in controls (p < 0.001). Treatment with 10(-7) M FP significantly reduced IL-13 production in healthy subjects and asthmatic patients both at 48 h (93.6 +/- 18.9 versus 50.50 +/- 10.6 pg/ml, p < 0.001, and 111.0 +/- 25.1 versus 59.3 +/- 13.6 pg/ml, p < 0.001, respectively) and at 72 h (63.9 +/- 9.6 versus 35.5 +/- 4.4 pg/ml, p < 0.001, and 73.3 +/- 8.0 versus 40.7 +/- 4.5 pg/ml, p < 0.001, respectively). Similar results were obtained with 10(-8) M FP at 48 and 72 h. Accordingly, evaluation of RT-PCR products from selected cell samples showed a FP dosage-dependent inhibition of IL-4 and IL-5 mRNA production both for healthy subjects and asthmatic patients. CONCLUSIONS: FP in vitro impairs IL-13 production by PHA-stimulated MNC from asthmatic and control subjects. This strengthens previous suggestions that IL-13 inhibition by steroids may, at least in part, account for their therapeutic effects.

Measurement of inflammatory mediators of eosinophils and lymphocytes in blood in acute asthma: serum levels of ECP influence the bronchodilator response.

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting beta(2)-agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV(1)) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV(1) from baseline [CD10, i.e. cumulative doses of salbutamol (800 microg) causing an improvement in FEV(1) from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a DeltaFEV(1) (percentage of predictive value of FEV(1)) of > or =10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 microg of salbutamol, significant differences of FEV(1) with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV(1) between the doses of salbutamol was observed. Significant differences of DeltaFEV(1) between 200 and 400 microg (p = 0.0002) and between 200 and 800 microg (p < 0.0001) were observed, but not between 400 and 800 microg of salbutamol. There were significant correlations between baseline values of predictive FEV(1) and serum ECP levels (rho = -0.60, p < 0.0001) and sIL-2R levels (rho = -0.35, p = 0.01) respectively. Besides, a correlation between DeltaFEV(1) and serum ECP levels (rho = -0.53, p < 0.0001) was observed, whereas no correlation was found between DeltaFEV(1) and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.