Action Of Disodium Cromoglycate Research Articles

Effect of disodium cromoglycate on inflammatory cells bearing the Fc epsilon receptor type II (Fc ϵRII)

Disodium cromoglycate (DSCG) has well-established stabilizing properties on mast cells and basophils. However, the potential inhibitory effect of DSCG has been little demonstrated on the IgE stimulation of cell populations expressing epsilon receptors type II, (Fc ϵRII), such as mononuclear phagocytes, eosinophils or platelets. Therefore, using various parameters of IgE-mediated triggering, we demonstrated the inhibitory role of DSCG on: (i) the release of neutrophil chemotactic factor by human alveolar macrophages, (ii) the oxygen metabolite-dependent chemiluminescence of human alveolar macrophages, rat peritonal macrophages, human eosinophils, human and rat platelets, and (iii) the β-glucuronidase release and synthesis by human alveolar macrophages. The inhibition of IgE-dependent stimulation ranged from 60% to 80%, according to the cells and to the measured parameter. It could therefore be considered that the action of DSCG was not restricted to its effects on mast cells and basophils, but also on other cells expressing Fc ϵR leading to a potential reduction of the physiopathological consequences of allergic asthma and, possibly, of the late phase reaction sometimes associated with the disease, insofar as these cells are involved.

The action of disodium cromoglycate on allergen-induced bronchoconstriction.

The influence of DSCG administered to the upper and lower area of the air-conducting system on antigen-induced bronchoconstriction was studied in 34 dogs. In high doses DSCG administered to the upper airtract blocked bronchoconstriction and histamine release induced from the lower airways. Bronchoconstriction and histamine release originating from the upper airtract were not completely blocked by this kind of drug administration. Effects were differently strong in the individual animals. High doses of DSCG, administered to the lower airways, showed significant effect on bronchoconstriction originating from the lower airways. There was some yet nonsignificant effect on histamine release. Inhibition of respiratory activity without parallel inhibition of histamine release might suggest that plasma histamine concentration does not reflect the mode of action of DSCG in antigen-induced bronchoconstriction.

Stimulation of contact sensitivity to oxazolone by disodium cromoglycate.

The subcutaneous administration of 0.01-10 mg/kg of the antiallergic agent disodium cromoglycate on day 0 30 min prior to sensitization of C57Bl/6 male mice with 5% 2-phenyl-4-ethoxy-methylene oxazolone proved to cause a significant stimulation of the low-grade volume response as measured plethysmographically in 24 h after challenge. The investigation of the mechanism favors the conclusion that histamine release is involved in the action of disodium cromoglycate as judged by the ability of the antihistaminics chlorpheniramine and metiamide to inhibit the disodium cromoglycate action and by the inhibitory effect of polymyxin B induced depletion of histamine.

A protective action of disodium cromoglycate against the contraction of guinea-pig ileum induced by various pharmacological stimulants.

The effect of disodium cromoglycate (DSCG) on the contraction of isolated guinea-pig ileum induced by histamine, acetylcholine and serotonin has been investigated. DSCG protected ileum against all agents tested. The action of DSCG at concentrations of 10(-3) to 10(-2) M was both dose- and time-dependent. Furthermore, DSCG inhibited compound 48/80-induced histamine release from isolated mast cells over the same range of concentrations. The anti-histaminic action of DSCG was reversible and after 2 h the ileum responded normally to histamine. DSCG-induced inhibition of the contractile response to histamine could be overcome by increasing concentrations of histamine but not by extracellular calcium. A mechanism of the action of DSCG, either against the contraction of ileal smooth muscle or against histamine release from mast cells, is discussed with a view to the inhibition of the utilization of calcium ions by both cells.

Effect of disodium cromoglycate on lymphocyte response to antigen and mitogen.

The effect of disodium cromoglycate (DSCG) on the three following in vitro correlates of cell-mediated immunity has been studied: (1) Transformation of human peripheral blood lymphocytes after stimulation by an antigen, purified protein derivative and a mitogen, phytohaemagglutinin; (2) release of macrophage migration inhibitory factor, and (3) cytotoxic factor production, from these stimulated lymphocytes. At two non-toxic concentrations DSCG did not inhibit these three lymphocyte functions. These results suggest that DSCG's clinical effectiveness does not depend upon modulating cell-mediated immune response. The implications of these findings in relation to present concepts of the cellular action of DSCG and the intracellular control of the initiation of lymphocyte transformation are discussed.

The Anti-Anaphylactic Actions of Disodium Cromoglycate, Theophylline, Isoprenaline and Prostaglandins

Various drugs used in the treatment of either allergy or inflammation have been studied in the rat. Prausnitz-Küstner (PK) type reactions, passive cutaneous anaphylaxis (PCA) and peritoneal mast cell degranulation (MCD) were used as models of type I anaphylactic hypersensitivity. In the PK test, the rank order of potency of the drugs tested was isoprenaline > PGF<sub>2α</sub> > disodium cromoglycate (DSCG) > indomethacin > theophylline. In the PCA test, the rank order was similar, although the difference between the potencies of DSCG and indomethacin was greater here than in the PK reaction. Dibutyryl cyclic AMP was inactive in both forms of cutaneous anaphylaxis. Noradrenaline, imidazole and propranolol induced MCD. Marked inhibition of phospholipase-A-induced degranulation occurred in the presence of DSCG, theophylline, indomethacin, dibutyryl cyclic AMP, aspirin, propranolol and phentolamine. Isoprenaline and prostaglandins E<sub>1;</sub> E<sub>2</sub> and A<sub>1</sub> all slightly inhibited MCD over a wide range of concentrations. Isoprenaline was synergistic with DSCG and theophylline in both PCA and MCD, and PGE<sub>1</sub> was synergistic with both DSCG and theophylline in MCD. However, there was no synergism between DSCG and theophylline or between isoprenaline and PGE<sub>1</sub>. The role of cyclic AMP in allergic reactions of the rat is discussed as is the mode of action of DSCG.