Novel clinical and serological aspects in non-allergic asthma.

BACKGROUND: We have recently observed that skin reactivity to autologous serum injection is common in patients with non-allergic asthma. However, clinical significance of skin reactivity to autologous serum remains to be defined. OBJECTIVE: To evaluate the possible relation between skin reactivity to autologous serum and clinical and laboratory characteristics in a series of patients with non-allergic asthma. METHODS: Fifty-five patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using basophils from a normal donor. Clinical and laboratory characteristics including peripheral blood eosinophilia, antinuclear antibodies and total IgE concentration were evaluated. As control, ASST was performed in 10 allergic asthmatic patients, 10 patients with allergic rhinitis and 10 normal subjects. RESULTS: ASST was positive in 29/55 non-allergic asthmatics (53%), whereas it was negative in all 30 control subjects (P<0.001). The sera of 6 out of 51 patients induced in vitro histamine release from autologous basophils. The sera from two patients induced histamine release from membrane IgE-stripped basophils. A significant predominance of female sex (83%) and a high incidence of antinuclear antibodies (ANA) positivity (55%) were found among ASST-positive patients. CONCLUSION: These findings indicate that ASST is positive in about half patients with non-allergic asthma and that a proportion of patients (16%) has functional evidence of circulating histamine-releasing factors. In addition, predominance of female sex and frequent ANA positivity are in line with an autoimmune basis of non-allergic asthma.

Autologous serum skin test reactivity in patients with non-allergic asthma.

BACKGROUND: Inflammatory alterations of respiratory airways have been found in patients with non-allergic asthma, but the triggering event has not been defined. An autoimmune activation of inflammatory cells has been hypothesized. OBJECTIVE: To evaluate whether histamine-releasing factors are present in sera from non-allergic asthmatics. METHODS: Twenty-four patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using autologous basophils as well as basophils from normal donors. Twenty-seven subjects with respiratory allergy and three normal subjects were chosen as control. RESULTS: ASST was positive in 14/24 non-allergic asthmatics (58%) whereas it was negative in all 30 control subjects (P<0.001). The serum of only one ASST-positive patient out of 12 (8.4%) induced in vitro histamine release from autologous basophils. The serum from another ASST-positive patient induced histamine release from membrane IgE-stripped autologous basophils. Sera from either non-allergic asthmatics or from control subjects did not provoke significant histamine release from basophils from three normal donors. CONCLUSION: Skin reactivity to autologous serum is common among non-allergic asthmatics, indicating the presence of circulating histamine-releasing factors. However, only in a minority of patients in vitro functional evidence of histamine-releasing autoantibodies (anti-FcepsilonRI or anti-IgE) was obtained. The presence of circulating histamine-releasing factors might contribute to initiation/maintenance of inflammation in respiratory airways of non-allergic asthmatics.

Prevalence and risk factors for latex allergy: a cross sectional study on health-care workers of an Italian hospital.

OBJECTIVES: The aim of this study was to determine prevalence and risk factors for latex hypersensitivity among health care workers (HCW) of an Italian general hospital. METHODS: 1747 HCW of the Ospedale Maggiore Policlinico of Milan were asked to fill in a questionnaire regarding latex-related manifestations (LRM) and personal medical history, and latex-specific IgE were measured by RAST-Cap system. RESULTS: 672 out of 1747 HCW (38.4%) answered to the questionnaire. LRM were reported by 168 out of 672 HCW (25%). The most common manifestation was hand dermatitis and itching (86.3%), followed by urticaria (3.5%) and respiratory symptoms (2.9%). Among the HCW with LRM, 75 (44.6%) reported a personal history of atopy and 24 (14.3%) reported oral allergy syndrome. most commonly related to kiwi, tomato, peach and melon/watermelon. Latex-specific IgE were found in 62 out of 1747 HCW (3.6%). Among the subjects answering the questionnaire, latex-specific IgE positivity was associated with occurrence of LRM (most commonly allergic contact dermatitis) and a longer professional exposure. The risk of latex IgE sensitisation was four times higher in HCW reporting atopic manifestations than in HCW without atopic disorders. Prevalence of LRM and latex-specific IgE was significantly higher among workers of auxiliary staff than among other job categories. The highest latex-specific IgE levels were found in subjects with severe latex-related symptoms and a personal history of atopy. CONCLUSIONS: A high prevalence of LRM was found among the HCW of an Italian general hospital, although a true latex sensitisation was detected only in a minority of cases. Members of the auxiliary staff, who wear latex gloves for several hours a day, had an increased prevalence of LRM and latex sensitisation. Atopy was a major risk factor for LRM and latex-specific IgE response.

Onset of allergy and asthma symptoms in extra-European immigrants to Milan, Italy: possible role of environmental factors.

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.

Chronic urticaria: novel clinical and serological aspects.

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 degrees 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 degrees C x 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 < 100 kDa were not able to induce any histamine release. Heparin dose-dependently inhibited histamine release induced by sera and plasma, and by basophil agonists such as anti-IgE, formyl-methionyl-leucyl-phenilalanine, and interleukin (IL)-3. CONCLUSIONS: 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked difference between in vivo and in vitro findings could reflect the existence of a mast cell-specific histamine-releasing factor which does not release histamine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil donors. At least in some cases complement seems essential for histamine-releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (in vivo), probably acting directly at a cellular level.

Effects of protein kinase C and phospholipase C inhibitors on IgE-dependent and IgE-independent basophil histamine release.

OBJECTIVE AND DESIGN: This study was aimed to evaluate the effects of two protein kinase C (PKC) inhibitors (staurosporine and chelerythrine) and one phospholipase C (PLC) inhibitor (U73122) on basophil histamine release induced by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), IL-3 and GM-CSF. METHODS: Leukocytes were suspended in solutions containing physiological or low Na+ concentrations, since IL-3 and GM-CSF were shown to induce histamine release only when the inhibitory effect of extracellular Na+ has been removed. After incubation with PKC and PLC inhibitors, the stimuli were added and histamine release was measured by an automated fluorometric method. RESULTS: Staurosporine and chelerythrine exerted a significant inhibitory effect on histamine release induced by anti-IgE, IL-3 and GM-CSF at concentrations much higher than those required to inhibit PKC. FMLP-induced histamine release in a physiological Na+-containing medium was not significantly modified by staurosporine, although it was reduced by high concentrations of chelerythrine. A slight inhibition by high concentrations of staurosporine was found when basophils were suspended in a low Na+ medium. U73122 exerted a significant and dose-dependent inhibitory effect on basophil histamine release induced by anti-IgE, FMLP, IL-3 and GM-CSF. CONCLUSION: These results suggest that a prodegranulatory role of PKC in basophil histamine release induced by anti-IgE, FMLP, IL-3 and GM-CSF is unlikely; conversely, it is conceivable that PLC has a role in signal transduction and histamine release induced by the above stimuli.

Inhibition of basophil histamine release by tyrosine kinase and phosphatidylinositol 3-kinase inhibitors.

It has been demonstrated that tyrosine kinase (TK) and phosphatidylinositol 3-kinase (PI3-K) are involved in IgE-mediated stimulation of human basophils; conversely, little is known about the biochemical pathways activated by IL-3 and GM-CSF. The aim of this study was to evaluate the effects of TK and PI3-K inhibitors on basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. Since IL-3 and GM-CSF cause histamine release from normal human basophils only when the inhibitory effect of extracellular Na(+) has been removed, peripheral blood leukocytes were suspended in isotonic solutions containing either 140 mM NaCl or 140 mM N-methyl-D-glucamine(+). After stimulation with anti-IgE, IL-3 or GM-CSF, histamine release was measured by an automated fluorometric method. The effects of preincubation with four different TK inhibitors (AG-126, genistein, lavendustin A, tyrphostin 51) and one PI3-K inhibitor (wortmannin) were evaluated. AG-126, genistein and lavendustin A exerted a significant dose-dependent inhibitory effect on basophil histamine release induced by anti-IgE (either in high or in low Na(+) medium), IL-3 and GM-CSF. Among the TK inhibitors, lavendustin A exerted the most potent activity, followed by AG-126 and genistein. Tyrphostin 51 caused a weak inhibition of histamine release induced by IL-3, GM-CSF and anti-IgE in a low Na(+) medium, but not in a physiological Na(+)-containing medium. The PI3-K inhibitor wortmannin exerted the most effective inhibitory activity on the histamine release induced by the three agonists. The combined effects of lavendustin A and wortmannin were less than additive, suggesting that TK and PI3-K are involved in the same activation pathway in human basophils. These results suggest a possible role of TK and PI3-K in basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. TK and PI3-K are indeed potential therapeutic targets for antiallergic drugs.

Chronic systemic capillary leak syndrome. Report of a case and review of the literature.

Systemic capillary leak syndrome (SCLS) is a rare condition characterized by recurrent episodes of generalized oedema and severe hypotension, associated with paraproteinaemia. In addition to the acute form, a few cases of chronic SCLS have been reported. We describe a 64-year-old woman who was hospitalized because of a 6-month history of progressive generalized oedema with pericardial and pleural effusions, associated with a serum paraprotein. Clinical and laboratory findings were consistent with a chronic form of SCLS. Treatment with prednisone, furosemide and theophylline was started, which led to a gradual improvement in 2 weeks and a persistent remission after 9 months. This report indicates that SCLS may occur in a chronic form, which seems to be responsive to a therapeutic regimen with prednisone, furosemide, and theophylline.

Favourable outcome of a case of pulmonary Langerhans' cell histiocytosis.

Pulmonary Langerhans' cell histiocytosis and eosinophilic granuloma are the terms used to describe a Langerhans' cell granulomatous interstitial lung disease of unknown aetiology, occurring predominantly in smokers and involving primarily lungs, bones, skin and lymph nodes. In this report a patient with fever, fatigue, dyspnoea, nocturnal perspiration and thoracic pain is described. The high-resolution computed tomography of the chest and histological examination of lung biopsies suggested the diagnosis of pulmonary Langerhans' cell histiocytosis. The disease was limited to the lung, since further investigations did not show any other localization. The patient had a good clinical outcome with avoidance of smoking and steroid therapy. The computed tomography scan follow-up showed a partial resolution of pulmonary lesions.

Sarcoidosis in a patient with 5q-myelodysplasia. A possible pathogenetic link between the two diseases.

This study describes the occurrence of sarcoidosis with lung and skin involvements in a 56-yr-old woman who suffered from 5q-myelodysplastic syndrome since the age of 50. The 5q-myelodysplastic syndrome is marked by deletion of the long arm of chromosome 5, which carries the genes coding for T-helper cell 2 cytokines, such as interleukins-3, -4 and -5, and granulocyte-macrophage colony-stimulating factor. Although the aetiology of sarcoidosis remains unclear, sarcoid granulomatous inflammation is marked by predominant expression of T-helper cell 1 cytokines, with reduced expression of T-helper cell 2 cytokines. The authors suggest that 5q-abnormality may have predisposed to sarcoidosis through an imbalance in the cytokine network, caused by the deletion of genes coding for T-helper cell 2 cytokines.

Nasal response to a single antigen challenge in patients with allergic rhinitis - inflammatory cell recruitment persists up to 48 hours.

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 and interleukin-3 cause basophil histamine release by a common pathway: downregulation by sodium.

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+.

N-acetyl-aspartyl-glutamic acid inhibits cellular recruitment and mediator release during the late allergen-induced nasal reaction.

OBJECTIVE: N-acetyl-aspartyl-glutamic acid (NAAGA) was effective in the treatment of allergic rhinitis, with an action on early allergen-induced nasal symptoms and mediator release. The aim of this study was to evaluate the clinical activity of NAAGA and its effects on the late antigen-induced reaction in the nose. METHODS: Ten patients with allergic seasonal rhinitis were included in this randomized double-blind crossover trial of a 6% wt/vol solution of NAAGA (daily dosage 84 mg) versus placebo (lactose). The drug and placebo were administered intranasally five times daily for 1 week, with a 2-week interval between treatments. RESULTS: Treatment with NAAGA, but not with placebo, significantly reduced the late antigen-induced nasal symptoms, mainly nasal obstruction. Eosinophil numbers in the nasal lavages collected 6 h and 24 h after challenge were significantly lower after NAAGA than after placebo. Active treatment also significantly reduced the neutrophil count 6 h after antigen challenge, and significantly lowered eosinophil cationic protein and myeloperoxidase levels in nasal lavages 6 h and 24 h after antigen challenge. CONCLUSION: These results indicate that treatment for 1 week with NAAGA can reduce the late antigen-induced reaction in the nose. This is accompanied by a reduction in eosinophil and neutrophil recruitment and release of eosinophil cationic protein and myeloperoxidase.

Reduced priming effect of interleukin 3 on IgE mediated basophil histamine release in patients with systemic sclerosis.

OBJECTIVE: To determine the capacity of interleukin 3 (IL-3) to induce and enhance basophil histamine release in patients with systemic sclerosis (SSc). METHODS: Leukocyte suspensions prepared by dextran sedimentation of peripheral venous blood were stimulated with anti-IgE (10 microg/ml), N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 microM), and IL-3 (0.1 to 10 ng/ml). The priming effect of IL-3 on anti-IgE and fMLP induced histamine release was evaluated. Histamine release was measured by an automated fluorometric method. RESULTS: No significant difference was found between patients with SSc (n = 12) and control subjects (n = 16) regarding spontaneous IL-3 and fMLP induced histamine release. IL-3 was a weak basophil agonist in both populations, since net histamine release did not exceed 10% of total histamine content in any case. Anti-IgE induced histamine release was lower in patients with SSc than in controls (13.09 +/- 4.8 vs 30.2 +/- 6.2%; p = 0.048). IL-3 enhanced anti-IgE and fMLP induced histamine release in a dose dependent fashion. However, the enhancement of anti-IgE induced histamine release by IL-3 was significantly lower in patients with SSc than in controls (p < 0.01 at 0.1 ng/ml IL-3; p < 0.05 at 1 and 10 ng/ml IL-3). In contrast, no difference was found between the 2 populations regarding the enhancement of fMLP induced histamine release by IL-3. CONCLUSION: Basophil response to anti-IgE and the priming effect of IL-3 on IgE mediated basophil histamine release are lower in patients with SSc than in controls. These alterations could be related to chronic activation of the IgE/basophil system in patients with SSc.

Fibrillary glomerulonephritis in Castleman's disease.

Castleman's disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castleman's disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.

In vivo and ex vivo inhibitory effects of loratadine on histamine release in patients with allergic rhinitis.

BACKGROUND: The aim of this study was to evaluate the in vivo and ex vivo effects of the H1-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 microg/ml), N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 microM), and Ca2+ ionophore A23187 (1 microM) was evaluated by an automated fluorometric method. RESULTS: Treatment with loratadine attenuated early antigen-induced 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 < 0.05). After treatment with loratadine, histamine release in the 5-min postchallenge lavages was almost abrogated (median 0.5 ng/ml, range 0-3; P < 0.01 vs placebo). Median anti-IgE-induced histamine release from basophils was 41.9% (range 27.8-79.2) after placebo and 30.0% (range 1.7-73.3, P < 0.05) after loratadine. Active treatment exerted an inhibitory effect also on basophil histamine release induced by fMLP and Ca2+ ionophore A23187. CONCLUSIONS: Treatment for 1 week with loratadine reduces allergen-induced nasal symptoms and inhibits in vivo and ex vivo histamine release in patients with allergic rhinitis.

Priming and inducing effects of interleukin-3 on histamine release from cord-blood basophils.

The effect of interleukin-3 (IL-3) on histamine release from cord and adult blood basophils were evaluated. Leukocyte suspensions, obtained from adult patients with respiratory allergy (n = 15), normal adult subjects (n = 15), and neonates with (n = 15) and without (n = 19) atopic disposition, were stimulated with anti-IgE, fMLP, and IL-3. IgE-mediated histamine release was significantly higher in adult patients, either allergic or normal, than in neonates with or without atopic disposition. A trend toward higher fMLP-induced histamine release was found in allergic adult subjects. IL-3 had a weak direct histamine-releasing activity in allergic adult subjects and in neonates, but not in normal adult donors. A significant enhancing effect of IL-3 on histamine release induced by anti-IgE was observed in neonates with and without atopic disposition and in normal adult subjects, but not in atopic adult patients. IL-3 exerted a priming effect also when basophils were stimulated with fMLP, without any significant difference between neonates and adult subjects. Passive sensitization with IgE-rich serum resulted in a significant increase in anti-IgE-induced, but not in IL-3-induced, histamine release from cord-blood basophils. In conclusion, IL-3 primes cord-blood as well as adult blood basophils for a consecutive anti-IgE- or fMLP-induced histamine release and its activity is not limited by the low density of membrane IgE in cord-blood basophils.