Foreign body granulomatous inflammation increases the sensitivity of splenocytes to immunomodulation by 1,25-dihydroxyvitamin D 3

Abstract

1,25-dihydroxyvitamin D 3, the active metabolite of vitamin D, partially inhibits antigen and mitogen-driven lymphocyte stimulation. We studied the effect of granulomatous inflammation on the sensitivity of lymphocytes to 1,25-dihydroxyvitamin D 3 in vitro, measuring the inhibitory effect of 1,25-dihydroxyvitamin D 3 on mitogenesis of splenocytes of mice with chronic inflammation induced by subcutaneous injection of talc. Systematic manifestations of the local inflammation included loss in body weight, splenomegaly, enhanced DNA synthesis by freshly isolated splenocytes and enhanced prostaglandin secretion by activated splenocytes. Splenocytes from animals with local inflammation were more susceptible to inhibition by 1,25-dihydroxyvitamin D 3, but not by prosaglandin E 2. This increased sensitivity to 1,25-dihydroxyvitamin D 3 was abolished by blocking prostaglandin synthesis in splenocyte cultures with indomethacin and was restored by adding prostaglandin E 2. This effect cannot be attributed to enhanced prostaglandin synthesis in the presence of 1,25-dihydroxyvitamin D 3, but is probably due to a qualitative change in the response of splenocytes from inflamed animals to the combined action of 1,25-dihydroxyvitamin D 3 and prostaglandin E 2.