In vitro study of the potential role of guanidines in leukocyte functions related to atherogenesis and infection

Kidney Int. 2004 Jun;65(6):2184-92. doi: 10.1111/j.1523-1755.2004.00631.x.


Background: The blunted immune response upon stimulation in chronic renal failure (CRF) is often coupled to a baseline inflammatory status which has been related to atherogenesis. Uremic biologic fluids and several specific uremic retention solutes alter cell-mediated immune responses, as well as the interaction of calcitriol with the immune system.

Methods: The present study evaluated the influence of different guanidino compounds on DNA synthesis, chemiluminescence production, and CD14 expression of undifferentiated and calcitriol-differentiated HL-60 cells. In a second setup, these guanidino compounds were evaluated for their specific effect on normal human leukocyte oxidative burst activity and tumor necrosis factor-alpha (TNF-alpha) expression.

Results: First, several guanidino compounds elicited proinflammatory effects on leukocytes. Methylguanidine and guanidine stimulated the proliferation of undifferentiated HL-60 cells and the antiproliferative effect of calcitriol (P < 0.05) was neutralized in the presence of methylguanidine (P < 0.05) and guanidinosuccinic acid (P < 0.05). The phorbol-myristate-acetate (PMA)-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was enhanced in the presence of guanidine (P < 0.05). Methylguanidine and guanidinoacetic acid enhanced the lipopolysaccharide (LPS)-stimulated intracellular production of TNF-alpha by normal human monocytes (P < 0.05). Second, several guanidino compounds inhibited the function of leukocytes if they were activated. The PMA-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was inhibited by the presence of methylguanidine (P < 0.05), guanidinoacetic acid (P < 0.05) and guanidinosuccinic acid (P < 0.05). After incubation of whole blood in the presence of methylguanidine, the Escherichia coli stimulated oxidative burst activity of the granulocyte population was significantly inhibited (P < 0.05). In addition, guanidinosuccinic acid had an inhibitory effect on the LPS-stimulated intracellular production of TNF-alpha by human monocytes (P < 0.01).

Conclusion: Guanidino compounds exert proinflammatory as well as anti-inflammatory effects on monocyte/macrophage function. This could contribute to the altered prevalence of cardiovascular disease and propensity to infection in patients with CRF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteriosclerosis / etiology*
  • DNA / biosynthesis
  • Guanidines / metabolism
  • Guanidines / toxicity*
  • HL-60 Cells
  • Humans
  • In Vitro Techniques
  • Infections / etiology*
  • Leukocytes / drug effects*
  • Leukocytes / physiology*
  • Luminescence
  • Respiratory Burst / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology


  • Guanidines
  • DNA
  • Tetradecanoylphorbol Acetate