Inhibition of in vitro allogeneic reactions with disodium cromoglycate

The antiallergic drug disodium cromoglycate (DSCG) selectively inhibits allogeneic responses in mixed lymphocyte culture (MLC) reactions, but does not affect cell viability or suppress lymphocyte responses to mitogens. Preincubation experiments with DSCG were without effect, indicating that the drug does not bind to unstimulated lymphocytes. Timed studies demonstrated maximal MLC inhibition when DSCG was added during the first 12 h or culture and no effect if added later than 72 h. Both natural killing and cell-mediated lympholysis (CML) assays proceeded normally in the presence of optimal MLC-inhibitory concentrations of DSCG. CML reactions were eliminated, however, by the presence of drug during generation of cytotoxic T cells. The proposed mode of action for DSCG is blocking of calcium influx across cell membranes, thereby inhibiting the release of mast cell and basophil granules in hypersensitivity reactions. Such a mechanism would seem unlikely for DSCG-mediated lymphocyte effects as several calcium-dependent lymphocyte functions are not obstructed.