The Effect of Homocysteine on the Secretion of Il-1β, Il-6, Il-10, Il-12 and RANTES by Peripheral Blood Mononuclear Cells-An In Vitro Study

Molecules. 2021 Nov 4;26(21):6671. doi: 10.3390/molecules26216671.

Abstract

The contemporary theory of the inflammatory-immunological pathomechanism of atherosclerosis includes the participation of interleukin-1β (Il), Il-6, Il-10, Il-12, RANTES, and homocysteine in this process. The knowledge on the direct effect of hyperhomocysteinemia on inflammatory-state-related atherosclerosis is rather scarce. Our study is the first to account for the effects of homocysteine on the secretion of Il-10 and RANTES in vitro conditions. For this purpose, human mitogen-stimulated peripheral blood mononuclear cells (PBMNCs) were cultured in vitro and exposed to homocysteine at high concentrations. Subsequently, the concentrations of cytokines were assayed in the cell culture supernatant using flow cytofluorimetry. It has been shown that, in the presence of homocysteine, the secretion of IL-1, IL-6 and RANTES by PBMNCs was increased, whereas IL-10 concentration was significantly lower than that of the supernatant derived from a mitogen-stimulated cell culture without homocysteine. The secretion of Il-12 by PBMNCs exposed exclusively to mitogen, did not differ from homologous cells also treated with homocysteine. Therefore, in our opinion, high-concentration homocysteine affects the progression of atherosclerosis by increasing the secretion of proinflammatory cytokines secreted by PBMNCs, such as Il-1β, Il-6, RANTES, and by attenuating the secretion of Il-10.

Keywords: Il-10; Il-12; Il-1β; Il-6; RANTES; homocysteine.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis*
  • Cytokines / biosynthesis*
  • Dose-Response Relationship, Drug
  • Homocysteine / pharmacology*
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism*

Substances

  • CCL5 protein, human
  • Chemokine CCL5
  • Cytokines
  • IL10 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • Homocysteine
  • Interleukin-10