FOREIGN-BODY GRANULOMATOUS INFLAMMATION INCREASES THE SENSITIVITY OF SPLENOCYTES TO IMMUNOMODULATION BY 1,25-DIHYDROXYVITAMIN-D3

1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, partiall y inhibits antigen and mitogen-driven lymphocyte stimulation. We studi ed the effect of granulomatous inflammation on the sensitivity of lymp hocytes to 1,25-dihydroxyvitamin D3 in vitro, measuring the inhibitory effect of 1,25-dihydroxyvitamin D3 on mitogenesis of splenocytes of m ice with chronic inflammation induced by subcutaneous injection of tal c. Systemic manifestations of the local inflammation included loss in body weight, splenomegaly, enhanced DNA synthesis by freshly isolated splenocytes and enhanced prostaglandin secretion by activated splenocy tes. Splenocytes from animals with local inflammation were more suscep tible to inhibition by 1,25-dihydroxyvitamin D3, but not by prostaglan din E2. This increased sensitivity to 1,25-dihydroxyvitamin D3 was abo lished by blocking prostaglandin synthesis in splenocyte cultures with indomethacin and was restored by adding prostaglandin E2. This effect cannot be attributed to enhanced prostaglandin synthesis in the prese nce of 1,25-dihydroxyvitamin D3, but is probably due to a qualitative change in the response of splenocytes from inflamed animals to the com bined action of 1,25-dihydroxyvitamin D3 and prostaglandin E2.