E. S. K. Assem

Inhibition of experimental asthma in man by a new drug (AH 7725) active when given by mouth.

A new drug, AH 7725, with properties similar to those of disodium cromoglycate (Intal) has the additional feature of being effective when taken by mouth. Six patients with allergic asthma were studied by bronchial challenge tests with antigen. In every one the drug was found to inhibit (either partially or completely) the immediate-type asthmatic response. Late responses were not influenced. The results were significant at the 0·5% level. These findings suggest that AH 7725 given by mouth may be able to inhibit naturally occurring asthmatic attacks in allergic patients. In this case its particular advantage as a prophylactic drug would lie in the treatment of very young asthmatic children and other patients who cannot take drugs by inhalation.

Stimulation of Histamine-Forming Capacity by Antigen in Sensitized Human Leucocytes

(1) Three types of experiments showed that histamine is formed during the reaction of antigen (D. pteronyssinus) with leucocytes of allergic human subjects: (a) total histamine of leucocytes (extracted + released) was increased; (b) histamine-forming capacity (HFC) of leucocytes was stimulated by antigen in vitro; (c) HFC of leucocytes was stimulated by injecting antigen in vivo. (2) Stimulation of HFC of leucocytes by antigen may provide a new and sensitive (though cumbersome) in vitro test of allergy.

Inhibition of allergic reactions by cromoglycate and by a new series of compounds (AH 6556, AH 7079 and AH 7725).

(1) A new series of anti-allergic drugs (AH 6556, AH 7079 and AH 7725) were shown to inhibit immediate-type allergy. They act by inhibiting release of pharmacological mediators, and they do not possess any bronchodilator activity. (2) Inhibition of allergic reactions was shown experimentally in a wide range of in vitro test models, and supports the findings in the preliminary in vivo studies in experimental animals. (2) The experimental evidence suggests that these compounds have some qualitative and quantitative advantages over disodium cromoglycate.

Release of thromboxane B2 and leukotriene C4 and reduction in renal perfusion in experimental anaphylactic reaction of isolated guinea pig kidney.

Isolated, perfused kidneys from ovalbumin-sensitized guinea pigs released large amounts of histamine, thromboxane (TX) B2 and less consistently leukotriene (LT) C4, and showed a marked reduction in perfusion rate (PR) following injection of the specific antigen, or antiserum to IgG1 and IgG2; both types of anaphylactic reaction being due to cross-linking of mast cell-sensitizing immunoglobulin. Infusion of low concentration of synthetic LTC4 caused reduction in PR, which was blocked by the antagonist FPL 55712. Large-dose bolus injections of histamine also reduced PR. It is concluded that the kidney is a target organ in anaphylaxis and that the reaction alters renal haemodynamics.

Demonstration of IgE-Sensitized Mast Cells in Human Heart and Kidney

We report the direct demonstration of IgE-bearing mast cells in human heart and kidney, as shown by immunohistochemical methods. This finding lends further support to the role of mast cells and IgE in the direct involvement of these two organs in immediate-type allergic reactions.

Investigation of the response to some haptenic determinants in penicillin allergy by skin and in vitro allergy tests

The role of three penicillin metabolites in human allergic reaction to penicillin has been assessed using sensitive in vitro tests in addition to skin testing. Conjugates of the benzylpenicilloyl (BPO), benzylpenicillenate (BPE) and penicillamine (PA) groups with human serum albumin (HSA) and bovine gamma globulin (BOG) have been made. In the passive haemagglutination test antibodies specific for all three determinants were found but there was no difference between allergic and non‐allergic groups. However, the ratio IgG/IgM, specific for each determinant, was higher in normals than in allergies. In skin tests, histamine release from leucocytes and the lymphocyte transformation test, the BPO group was confirmed as the major determinant, but in some individuals the BPE or PA groups are more important.

Inhibition of Allergic Reactions by Cromoglycate and by AH 7079 in Patients with Allergic Airway Disease

(1) A quantitative comparison was carried out between the inhibitory effects of disodium cromoglycate (DSCG) and a representative of a new series of anti-allergy compounds (AH 7079) on the response of patients with allergic asthma to allergen inhalation. (2) Asthmatic attacks due to immediate allergic response to experimentally inhaled antigen, were inhibited by AH 7079 inhaled shortly before antigen. A dose of 3 mg seemed to be optimal in this test. However, the single dose given did not inhibit late reactions. The relative potency of AH 7079 and DSCG in inhibiting the response to bronchial challenge was not reliably assessed because of the unusual shape of dose-response curves, particularly of DSCG. (3) Bronchial hyposensitization due to repeated allergen inhalation posed a big problem in assessing the effects of these inhibitors. Such a problem may be met with in similar studies of other drugs. The use of inhibitors may enhance the development of bronchial desensitization. (4) A double-blind trial of AH 7079 in patients with allergic rhinitis showed that this drug also inhibits reactions to nasal challenge with antigen. Our findings suggest that AH 7079 is a potent anti-allergy drug and that it can protect patients with allergic airway disease against reactions to antigen.