I. Bendror et al., FOREIGN-BODY GRANULOMATOUS INFLAMMATION INCREASES THE SENSITIVITY OF SPLENOCYTES TO IMMUNOMODULATION BY 1,25-DIHYDROXYVITAMIN-D3, International journal of immunopharmacology, 15(3), 1993, pp. 275-280
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.