Antigen‐induced Bronchial Anaphylaxis in Actively Sensitized Guinea‐pigs: Effect of Long‐term Treatment With Sodium Cromoglycate and Aminophylline

Abstract

The effects of long‐term treatment with sodium cromoglycate (SCG) and aminophylline on antigen‐induced bronchoconstriction have been studied in guinea‐pigs actively sensitized according to two different regimens (one producing IgE‐ and IgG‐like antibodies and the other producing exclusively IgG‐like antibodies). Treatment for three weeks with SCG (10 mg/kg) and aminophylline (10,30 or 60 mg/kg) led to a decreased bronchial response capacity which persisted even three days after treatment ceased. In this respect SCG was effective only in guinea‐pigs sensitized to produce at least partly IgE‐like antibodies; aminophylline was effective in guinea‐pigs sensitized to produce both IgE and/or IgG antibodies. The results in vivo with SCG were reflected in vitro by a reduced capacity of chopped lung tissue to release histamine at antigen challenge; lungs from animals treated with aminophylline did not show reduced histamine releasing capacity. Acute treatment with atropine was shown to reduce significantly the antigen‐induced bronchial contraction in guinea‐pigs sensitized to produce both IgE‐ and IgG‐antibodies. No effect of atropine was seen on an IgG‐mediated anaphylaxis. Increased reactivity to methacholine but not to histamine was seen in guinea‐pigs sensitized to produce both IgG‐ and IgE‐antibodies. Long‐term treatment with SCG did not affect this hyperreactivity to methacholine. Decreased reactivity to isoprenaline was found in isolated tracheae taken from guinea‐pigs sensitized to produce both IgE‐ and IgG‐like antibodies compared to unsensitized guinea‐pigs. Long‐term treatment with SCG, but not with aminophylline, reversed this decreased reactivity.

Histamine and leukotriene‐independent guinea‐pig anaphylactic shock unaccounted for by Paf‐acether

“…FPL 55712, which also failed to inhibit bronchoconstriction of anaphylaxis in animals sensitized in a system which favours IgE-dependent reactions (Andersson & Bergstrand, 1981), synergizes with an anti-histaminic agent to inhibit shock in propranololtreated animals sensitized with large doses of ovalbumin (Andersson et al, 1983;Lewis et al, 1983). Our results show that when low sensitizing doses of ovalbumin are used, FPL 55712 alone is inactive against bronchoconstriction in propranolol-treated animals but that its use in combination with mepyramine, methysergide and aspirin reduces bronchoconstriction by 60%.…”

“…Hartley guinea-pigs of either sex (300-500g) were injected subcutaneously with 0.5 ml of 0.9% w/v NaCI solution (saline) containing 10 tLg of ovalbumin dispersed in 1 mg of AI(OH)3 (modified from Andersson & Bergstrand, 1981). This injection was repeated after 14 days and the animals were used 21 -27 days after the first injection.…”

Effects of Inhibitors of Anaphylactic Mediators in Two Models of Bronchial Anaphylaxis in Anaesthetized Guinea‐pigs

“…As there are reports of IgG-mediated release of anaphylactic mediators like histamine and SRS-A from rat peritoneal mast cells (Moodley & Mongar, 1981) and guinea-pig lung in vitro (Andersson & Bergstrand, 1981;Forsberg & Sorenby, 1981), it seems reasonable to assume the release of histamine and SRS-A induced by IgG antibodies in the present investigation to be derived from mast cells. There are indications of separate receptors for IgG and IgE antibodies on mice mast cells (Daeron, ProuvostDanon & Voisin, 1980).…”

“…The respiratory measurements were performed as described earlier (Andersson & Bergstrand, 1981 Potential inhibitors of anaphylactic bronchoconstriction were administered at various times: FPL 55712 was given immediately before challenge; BW 755C was given intravenously 2 min before challenge; mepacrine, p-bromphenacylbromide, indomethacin and mepyramine were all given intravenously 5 min before challenge and budesonide was given intraperitoneally 15-20 h before challenge.…”

“…Furthermore, some important differences were shown between the anaphylactic reactions obtained in animals sensitized according to these two regimens. Thus higher provocation doses are needed to obtain an effect and much more histamine is released after anaphylactic challenge in guinea-pigs sensitized to produce a mixture of IgG and IgE antibodies compared with those sensitized to produce only IgG antibodies (Andersson, 1980a; 0007-1188/82/100301-07 $01.00 Andersson & Bergstrand, 1981). Furthermore, disodium cromoglycate (SCG) and glucocorticoids do not prevent IgG-mediated bronchial anaphylaxis (Andersson, 1980b; Andersson & Bergstrand, 1981; Andersson & Brattsand, 1982).…”