EFFECT OF HYDROCORTISONE AND DISODIUM-CROMOGLYCATE ON MAST CELL-MEDIATOR RELEASE INDUCED BY SUBSTANCE-P

Release of inflammatory mediators from mast cells following immunoglob ulin bridging by specific allergens triggers episodes of asthma and br onchial hyperreactivity. Recent evidence has shown that neuropeptides, such as substance P (SP), may modulate the pulmonary inflammatory res ponse in these airway diseases. This suggests that SP may affect secre tory events of mast cells. To investigate these effects, resident peri toneal mast cells were collected from Sprague-Dawley male rats and sti mulated with Con A (utilizes surface-bound immunoglobulin), compound 4 8/80 (acts in a peptide-like manner) and SP. Secretion was assessed as the release of preloaded [C-14]serotonin. All secretagogues induced d ose-dependent release. Pharmacologic modulation of release was then st udied with two drugs employed for treatment of airway disease, hydroco rtisone, a classical anti-inflammatory steroid, and disodium cromoglyc ate (DSCG). Following pretreatment with 5 mu mol/l hydrocortisone, ser otonin release induced by Con A was inhibited by 59%. No inhibition wa s noted with compound 48/80 or SP release. Similarly, following DSCG ( 300 mu mol/l) pretreatment, 40% inhibition of release was noted with C on A, but no inhibition occurred following compound 48/80- or SP-stimu lated release. Collectively, these results suggest that mast cells pos sess multiple activation-secretion coupling pathways which respond dif ferently to clinically used pharmacologic agents. Diseases involving S P modulation of mast cell mediator release may not be successfully tre ated with anti-inflammatory steroids or DSCG.