TGF-beta and TNF-alpha producing effects of losartan and amlodipine on human mononuclear cell culture

Nephrology (Carlton). 2005 Oct;10(5):478-82. doi: 10.1111/j.1440-1797.2005.00462.x.

Abstract

Aim: The modulation of cytokine release, which affects adhesion of leucocytes to endothelial cells, and proliferation of peripheral blood mononuclear cells with antihypertensive drugs was explored.

Method: In the present study, mononuclear cells were incubated with losartan and amlodipine at concentrations of 10(-6), 10(-5) and 10(-4) mol/L for 6 h. Transforming growth factor (TGF)-beta and tumour necrosis factor (TNF)-alpha levels were measured. Proliferation of mononuclear cells were assessed at the same concentrations of amlodipine and losartan with the methylthiazoletetrazolium (MTT) test.

Results: Amlodipine was found to induce TGF-beta synthesis from mononuclear cells with increasing concentrations, while it was found to inhibit TNF-alpha secretion with increasing concentrations. In contrast, losartan was found to induce TGF-beta and TNF-alpha secretion with increasing concentrations.

Conclusion: Anti-atherosclerotic effects of amlodipine and losartan might be through increased secretion of TGF-beta from mononuclear cells. Different results at different concentrations might be due to the pharmocokinetic differences of these drugs.

MeSH terms

  • Amlodipine / pharmacology*
  • Antihypertensive Agents / pharmacology*
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology
  • Cells, Cultured
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Losartan / pharmacology*
  • Transforming Growth Factor beta / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antihypertensive Agents
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Amlodipine
  • Losartan