Clofazimine and B669 inhibit the proliferative responses and Na+, K(+)-adenosine triphosphatase activity of human lymphocytes by a lysophospholipid-dependent mechanism

Biochem Pharmacol. 1993 Dec 3;46(11):2029-38. doi: 10.1016/0006-2952(93)90645-d.


The relationship between the phospholipase-stimulating and immunosuppressive properties of the riminophenazine anti-mycobacterial agent clofazimine and its experimental analogue, B669, has been investigated in vitro. At concentrations of 0.6 microM and upwards, both riminophenazines, particularly B669, caused dose-related inhibition of mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leucocytes (MNL), while in short-term assays both agents increased the release of lysophosphatidylcholine (LPC) and arachidonic acid from these cells. Arachidonate per se at a concentration of 20 microM did not affect mitogen-activated lymphocyte proliferation, while cyclooxygenase and 5'-lipoxygenase inhibitors, as well as water- and lipid-soluble oxidant-scavengers and anti-oxidant enzymes, failed to protect the cells against the anti-proliferative effects of clofazimine and B669. However, LPC caused dose-related inhibition of lymphocyte proliferation. Moreover, co-incubation of NML with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase, protected the cells against clofazimine and B669, as well as against LPC. Na+, K(+)-adenosine triphosphatase was identified as the primary target of riminophenazine/LPC-mediated inhibition of lymphocyte proliferation. Excessive release of anti-proliferative lysophospholipids during clofazimine or B669 treatment of mitogen- or antigen-activated lymphocytes is the probable biochemical mechanism of the immunosuppressive activity of these agents.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Arachidonic Acid / metabolism
  • Cell Division / drug effects
  • Clofazimine / analogs & derivatives*
  • Clofazimine / pharmacology*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lysophospholipase / metabolism
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology*
  • Phospholipases A / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / enzymology
  • Tritium
  • Vitamin E / chemistry


  • Anti-Infective Agents
  • Immunosuppressive Agents
  • Lysophospholipids
  • Tritium
  • Vitamin E
  • Arachidonic Acid
  • B 669
  • Clofazimine
  • Phospholipases A
  • Lysophospholipase
  • Sodium-Potassium-Exchanging ATPase