1,25-dihydroxyvitamin D₃ potentiates the decreased response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine monophosphate

The inhibitory effect of prostaglandin E₂, histamine, isobutylmethylxanthine, and 1,25-dihydroxyvitamin D₃ (1,25-[OH]₂D₃) on the mitogenic stimulation of peripheral blood lymphocytes from normal and atopic subjects was studied. We found that lymphocytes from atopic patients were less susceptible to inhibition by the three agents that elevate intracellular cyclic adenosine monophosphate (cAMP) concentrations and by the active metabolite of vitamin D (inhibition of 27%, 14%, 12%, and 36% for the atopic patients as compared with 40%, 20%, 22%, and 46% for the normal donors, by the four agents, respectively; p<0.02). The inhibitory effect of the cAMP-elevating agents was potentiated by the addition of 1,25-(OH)₂D₃ to the lymphocyte cultures. The potentiation was more pronounced on lymphocytes from the atopic donors, increasing their responsiveness to levels comparable to levels of lymphocytes from normal donors. The synthetic corticosteroid, dexamethasone, had a similar potentiating effect on the inhibitory action of prostaglandin E₂. In view of the beneficial action of β-agonists, phosphodiesterase inhibitors, and corticosteroids in the treatment of allergy, the potentiating effect of 1,25-(OH)₂D₃ on the action of cAMP.-elevating agents may be of therapeutic interest.