Furosemide inhibits in vitro histamine release induced by antigens and anti-IgE.

We used 56 samples of heparinized blood of patients with asthma and/or allergic rhinitis, which were stimulated with Dermatophagoides pteronyssinus or gramineous pollen and anti-IgE in order to study the effect of furosemide on histamine release in basophils. At the same time, blood samples incubated in furosemide in different concentrations (2.5 microM to 1.49 mM) were also subjected to the same stimuli. Results showed a linear and dose-dependent inhibition of histamine release for antigens (r = 0.96; p < 0.01) and anti-IgE (r = 0.95; p < 0.05), reaching 95% at maximum inhibition. These results support the hypothesis that furosemide may act on mastocytes and basophils, thus inhibiting the release of histamine and other mediators.

IgG4 blocking effect on the release of antigen-specific histamine.

We evaluated the biological effect of IgG4 antibodies in pollinosis. We studied the ability of IgG4 to mediate histamine release by measuring anti-IgG4 in pollinic patients without previous immunotherapy. We also evaluated the modifications that sera rich in specific IgG4 and IgG itself exert upon antigen-specific histamine release. According to our results, stimulation with anti-IgG4 did not induce histamine release, as opposed to stimulation with anti-IgE, which induced histamine release in all the cases studied. On the other hand, hyperimmune sera from pollinic subjects under immunotherapy and with high levels of specific IgG4 significantly inhibited the release of antigen-specific histamine from basophils of untreated patients. After isolating IgG4 by means of affinity chromatography, preincubation of this fraction with the allergen gave rise to a significant reduction in histamine release compared to preincubation of the antigen with normal sera.

Bronchial challenge with aspirin lysine in the diagnosis of asthmatics with sensitization to aspirin and its inhibition by aerosolized furosemide.

We performed bronchial challenge with ASA lysine in 9 patients with a history of aspirin-induced asthma, 4 asthmatics with no history of hypersensitization to aspirin and 4 control subjects. The test consisted of successive inhalations of increasing concentrations of ASA lysine (11.25, 22.5, 45, 90, 180 and 360 mg/ml) and was interrupted when FEV1 showed a decrease of at least 20%. In order to determine the degree of bronchial hyperreactivity, we first carried out a bronchial challenge with histamine. All patients in the group sensitive to aspirin had a positive reaction to ASA lysine, while this was negative for patients in the two control groups. There was no significant correlation between PC20 to histamine and ASA lysine in any of the groups. On the other hand, 6 patients with sensitivity to ASA repeated the bronchial challenge with ASA lysine after previously inhaling furosemide, and in this second test, none of the 6 had a positive reaction. The variation of ASA lysine PC20 in both tests was positive for these patients (p < 0.001).

Study of IgE-dependent basophil releasability in allergic patients.

For this study, venous blood from 160 patients with a diagnosis of asthma and/or rhinitis was used. Histamine release test (H.R.T.) with anti-IgE at 1/5 and 1/25 dilutions and with causal antigen in the case of atopic patients (144) was carried out on all patients. Basophils from atopic patients released more histamine than those from nonatopic patients (p < 0.001). Basophils of atopic patients released more histamine with 1/5 anti-IgE dilution (p < 0.01), while non-atopic patients did so with the 1/25 dilution (p < 0.05). On grouping atopic patients according to positive or negative results in Ag-specific histamine release, 14% of patients presented negative Ag-specific H.R.T. and 85.7% of the cases did not respond to anti-IgE stimulus; this was 12% of the total number of atopics. On the other hand, 17% of the patients studied did not show positive histamine release against anti-IgE and 70.6% of them had negative Ag-specific release. As for the effect of age on IgE-dependent histamine release, the group of patients who presented greater releasability corresponded to those older than 6 years of age. The discrepancies observed between the clinical history, skin tests, serum IgE and antigen-dependent histamine release in some patients could be related to the individual basophil ability to release histamine. Therefore, this basophil releasability evaluation has an important practical application in discerning false negatives in antigen-specific H.R.T.