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1,25-Dihydroxyvitamin D₃ and Agents that Increase Intracellular Adenosine 3',5'-Monophosphate Synergistically Inhibit the Mitogenic Stimulation of Human Lymphocytes^*

Rogoff Medical Research Institute (A.R., R.N., A. N), and Metabolic Diseases Unit (R.K., R.N., C.R., U.A.L.), Beilinson Medical Center Petah Tikva
the Sackler School of Medicine, Tel-Aviv University Tel-Aviv, Israel

Address requests for reprints to: Dr. A. Ravid, Rogoff Medical Research Institute, Beilinson Medical Center, Petah Tikva 49100, Israel.

1,25-Dihydroxyvitamin D₃ [1,25-(OH)₂D₃], like the immune response modulators prostaglandin E₂ (PGE₂) and histamine, inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. 1,25-(OH)₂D₃ acts synergistically with PGE₂ and histamine to inhibit lymphocyte mitogenesis. This is apparent at a wide concentration range of 1,25-(OH)₂D₃ (3 x 10^–11–10^–8 mol/L). Cholera toxin, forskolin, and isobutylmethylxanthine, which like PGE₂ and histamine increase intracellular concentrations of cAMP, also act synergistically with 1,25-(OH)₂D₃ in this system. Culture of mitogenstimulated adherent cell-depleted mononuclear cells with PGE₂ increases the number of high affinity binding sites for 1,25-(OH)₂D₃. This finding may account for the synergistic interaction between the two agents.

^* Presented in part at the Annual Meeting of the Society of Bone and Mineral Research, June 1987, and at the Seventh Workshop on Vitamin D, 1988. This work was supported by Grant 85–00276 from the U.S.-Israel Binational Science Foundation, Jerusalem, Israel.

Received September 5, 1989.