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Summary Background Allergy and asthma are typical disorders of the affluent societies. Migrants from developing to industrialized countries seem to be at increased risk of allergy and asthma development. Objective To evaluate time of onset, spectrum of sensitization and clinical features in a population of extra-European immigrants to Milan, Italy, complaining of allergy and asthma symptoms. Methods Data regarding 243 extra-European immigrants checked at an allergy clinic from 1994 to 2000 were collected retrospectively. The demographic data were compared with those of the extra-European immigrants living in Milan at the end of 1999. Results The patients were complaining of asthma (63.7%), rhinoconjunctivitis (56.7%), rhinitis alone (21%) or urticaria (3%). One hundred and eighty-seven out of 222 patients (84.3%) declared they were healthy before migrating and allergy/asthma symptoms started to appear after their arrival in Italy, namely after an average period of 4 years and 7 months. The proportion of male patients was lower than the proportion of men in the extra-European immigrant population (48% vs. 55%), suggesting that in adult immigrants allergy and asthma are more common in women than in men. Furthermore, there was an over-representation of Central-South Americans attending the clinic, which seemed to be due to a genetic predisposition to allergy/asthma development. When data were analysed for single countries, a trend towards an increased risk of allergy and asthma was found in immigrants from all Central-South American countries. A skin test positivity for at least one inhalant allergen was found in 196 out of 232 patients (81%), and the spectrum of allergic sensitization was similar to that of the Italian population living in the North of Italy. Conclusion Most extra-European immigrants declared that they were healthy at home and that allergy and asthma symptoms had appeared after immigration to Milan; lifestyle and environmental factors in a western industrialized city seem indeed to facilitate allergy/asthma onset in immigrants from developing countries. Allergy/asthma risk seems to be different in different ethnic groups.

Background Recently, distinct studies have shown that: (a) chronic idiopathic urticaria (CIU) is autoimmune in 30–50% of cases; (b) in patients with CIU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement-dependent. Objective To carry out a comprehensive clinical and serological study on CIU based upon these observations. Methods Three hundred and six adults with CIU underwent intradermal (ID) test with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in vitro histamine release from basophils of normal donors. The effects of heating (56 °C, 60 min), filtration through membrane, and preincubation with heparin were evaluated as well. Results Autologous serum and plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Positive plasma skin tests were observed only in patients showing strongly positive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patients with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release from basophils of normal donors. 19/20 sera were from patients with a positive intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 °C × 1 h markedly reduced the histamine-releasing activity of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine-releasing activity, whereas fractions

Background Allergen challenge in some patients with respiratory allergy is followed by an early and a late reaction. Objective To evaluate the duration of mediator release and inflammatory cell recruitment during the late antigen-induced nasal response. Methods Eight patients with seasonal allergic rhinitis due to grass pollen underwent local challenge with the relevant allergen, a non-relevant allergen (Parietaria judaica), and nebulized saline solution. Nasal lavages were performed at baseline and 6, 24, 48, 72 h after challenge. Eosinophil cationic protein (ECP), leukotriene C4 (LTC4), leukotriene B4 (LTB4) myeloperoxidase (MPO) and prostaglandin D2 (PGD2) levels were radioimmunoassayed and histamine concentration was measured by an automated fluorometric method. Results Nasal challenge with the relevant antigen induced a response 6 h after stimulation, which subsided within 24 h. Eosinophilia, observed in the nasal lavages collected from 6 to 24 h after this challenge, was accompanied by ECP release. Neutrophilia were found in the nasal lavages collected from 6 to 24 h after challenge. The increase in neutrophil number correlated with MPO levels and LTB4 concentrations, but not with the intensity of nasal obstruction. Antigen challenge also induced significant recruitment of mononuclear cells 48 h after provocation. The challenge significantly raised histamine, but not PGD2, levels in the nasal lavages collected 6 h after provocation. A trend towards an increase in LTC4 levels in the nasal lavages collected 6 h after specific antigen challenge was also found. Nasal challenge with a non-relevant allergen or with saline solution did not cause either inflammatory cell recruitment or mediator release. Conclusion Nasal challenge with the relevant antigen can induce a late response characterized by local accumulation of eosinophils, neutrophils and mononuclear cells persisting for 48 h and accompanied by release of ECP, MPO, LTB4 and histamine. These results indicate that a single antigen challenge in patients with allergic rhinitis causes prolonged inflammatory alterations which may contribute to the development of airway hyperreactivity.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are recognized as enhancers, but not as inducers, of histamine release from normal human basophils. However, when extracellular Na+ is removed IL-3 acquires the capacity to induce histamine release. The aim of this study was to evaluate whether GM-CSF can induce basophil histamine release using the same pathway of IL-3. Leucocyte suspensions from normal human subjects were stimulated with GM-CSF, IL-3 and anti-IgE, and histamine release was evaluated by an automated fluorometric method. In a physiological medium, GM-CSF (10 ng/ml) and IL-3 (10 ng/ml) did not provoke histamine release, in spite of an efficient response to anti-IgE (10 micrograms/ml). However, when extracellular Na+ was substituted iso-osmotically with N-methyl-d-glucamine+ or with choline+, GM-CSF and IL-3 were able to trigger histamine release from either mixed leucocyte suspensions or purified human basophils. The effect of GM-CSF on basophil histamine release was dose dependent, with optimal release at a dose of 1 ng/ml after incubation at 37 degrees for 60-120 min. The kinetics of IL-3-induced histamine release were similar, whereas anti-IgE-induced histamine release was more rapid, being almost maximal after incubation for 30 min. A good correlation was found between GM-CSF-induced and IL-3-induced histamine release; furthermore, the combined effects of the two cytokines were less than additive, suggesting that they share the same pathways leading to histamine release. When extracellular Na+ concentration was increased from 0 to 140 mm, histamine release induced by GM-CSF, IL-3 and anti-IgE was reduced progressively. In contrast, histamine release induced by these stimuli was upregulated when the concentration of extracellular Ca2+ was increased. These results provide indirect evidence that GM-CSF and IL-3 can induce basophil histamine release by a common pathway that is downregulated by Na+.

Background The aim of this study was to evaluate the in vivo and ex vivo effects of the H.-antagonist loratadine on histamine release. Methods The study was designed as a double-blind, crossover trial. Ten patients with allergic rhinitis due to Dermatophagoides pteronyssinus were treated with loratadine (10 mg daily p.o.) and with placebo for 1 week, with a 2-week interval between the two treatments. Nasal lavages with saline solution were done before and after challenge with the relevant allergen at the end of treatments with loratadine and placebo. Venous blood was taken after treatments, and basophil histamine release induced by anti-IgE (10 μg/ml), N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 μM). and Ca2+ ionophore A23187 (1 μM) was evaluated by ati automated fluorometric method. Results Treatment with loratadine attenuated early antigen-tnduced nasal obstruction, rhinorrhea. and itching. Nasal symptoms were accompanied by a significant histamine release in the nasal lavages collected 5 min after stimulation when the patients received placebo (median 4 ng/ml, range 1-28; P

The aim of this study was to evaluate whether Na+ exerts its inhibitory effect on basophil histamine release induced by immunoglobulin E (IgE)-dependent (anti-IgE) and IgE-independent (N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-3 (IL-3)) stimuli in patients with allergic rhinitis (n = 24) and allergic bronchial asthma (n = 10). Peripheral blood leucocytes were stimulated with anti-IgE, FMLP and IL-3 in the presence of high and low Na+ concentrations, and histamine release was measured using a fluorometric method. In standard Na(+)-containing medium, spontaneous and stimulated histamine release was higher in allergic patients (n = 34) (both rhinitic and asthmatic) than in healthy subjects (n = 41). Na+ removal from extracellular medium and its isosmotic substitution with choline chloride or with N-methyl-D-glucamine led to a significant increase of anti-IgE-, FMLP- and IL-3-induced histamine release in normal subjects, but not in allergic patients. The increase in Na+ concentration in the extra-cellular medium was accompanied by a dose-dependent decrease of anti-IgE- and FMLP-induced histamine release in normal subjects, but not in allergic patients. The behaviour of atopics and healthy subjects was different and not related to the basophil responsiveness to activating signals. The incubation of basophils from healthy subjects with sera from allergic patients did not have a significant influence on the inhibitory effect of Na+. Basophils from healthy subjects and atopic patients respond differently when stimulated in a low Na+ medium. The reduced sensitivity to the inhibitory effect of Na+ may contribute to basophil dysfunction in patients with respiratory allergy.

The inducing and enhancing effects of interleukin-3 (IL-3) on basophil histamine release in patients with respiratory allergy (n = 28) and in normal subjects (n = 22) were compared. Leukocyte suspensions, prepared by dextran sedimentation, were stimulated with anti-IgE (1/5000), N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM), and IL-3 (0.1-10 ng/ml), and histamine concentration was measured by an automated fluorometric method. A trend toward higher histamine release after challenge with anti-IgE, FMLP, and IL-3 was found in atopic subjects. Preincubation of basophils with IL-3 resulted in a dose-dependent increase of anti-IgE- and FMLP-induced histamine release, with a more marked effect in nonatopic than in atopic subjects. Mean net enhancement of anti-IgE-induced histamine release by 10 ng/ml IL-3 was 2.5 +/- 5% in atopic subjects and 29.6 +/- 4.2% in nonatopic subjects (P < 0.001). The enhancement of FMLP-induced histamine release by IL-3 was 10.3 +/- 3.9% in atopic patients and 29 +/- 2.4% in nonatopic subjects (P < 0.01). In atopic subjects, a negative correlation was found between anti-IgE- or FMLP-induced histamine release and net enhancement by IL-3 (r = -0.45, P < 0.02; r = -0.48, P < 0.01, respectively). The results of this study indicate that in atopic subjects IgE-mediated histamine release can scarcely be enhanced by a basophil response modifier such as IL-3. It is conceivable that the frequent basophil stimulation in atopic patients leads to a reduced sensitivity to the enhancing effect of IL-3.

Background Nasal challenge with platelet activating factor (PAF) is able to induced local neutrophilia, with a different degree of responsiveness in atopic subjects and in nonatopic subjects. We investigated whether nasal accumulation of neutrophils induced by PAF is accompanied by the release of neutrophil-derived mediators. Methods: Nasal lavages were performed before and after challenge with PAF (500 nmol), lyso-PAF (500 nmol), and saline solution in 10 patients with allergic rhinitis and 10 normal subjects to evaluate changes in neutrophil counts and the release of myeloperoxidase (MPO) and immunoreactive leukotriene B 4 . Results: PAF caused neutrophilia, which appeared after 30 minutes in atopic subjects and after 3 hours in nonatopic subjects. Furthermore, when compared with saline insufflation, PAF caused a significant release of MPO in the nasal lavage fluids collected 30 minutes, 3 hours, and 24 hours after challenge in atopic subjects and 3 hours after challenge in nonatopic subjects, with higher values in the former than in the latter. Neutrophil counts correlated with MPO levels in the nasal lavages collected after PAF challenge. A lower degree of neutrophilia was found 3 hours after stimulation with lyso-PAF in both groups of subjects, with a marginal release of MPO in atopic subjects only. No significant increase of immunoreactive leukotriene B 4 levels in nasal lavages was found after challenge with either PAF or lyso-PAF. Conclusion: These results indicate that PAF-induced neutrophilia in the nose is accompanied by the release of MPO, which appears earlier and is more marked in atopic subjects than in nonatopic subjects.