Piperine inhibits cytokine production by human peripheral blood mononuclear cells

Genet Mol Res. 2012 Mar 14;11(1):617-27. doi: 10.4238/2012.March.14.5.


Piperine, an amide isolated from Piper species (Piperaceae), has been reported to exhibit central nervous system depression, anti-pyretic and anti-inflammatory activity. Immunomodulatory and anti-tumor activity of piperine has been demonstrated in mouse carcinomas. However, there is little information available concerning the effect of piperine on humans. We evaluated the immunopharmacological activity of this compound in human immune cells. Human peripheral blood mononuclear cells (PBMCs) were exposed to piperine, and cell proliferation was determined by the MTS assay. Piperine significantly inhibited phytohemagglutinin-stimulated human PBMC proliferation after exposure for 72 h. This compound inhibited PBMC activity, with an IC(50) of 100.73 ± 11.16 μg/mL. Production of interleukin-2 (IL-2) and interferon-γ (IFN-γ) was measured using an ELISA assay and RT-PCR. Piperine inhibited IL-2 and IFN-γ production in the PBMCs. RT-PCR data indicated that IL-2 and IFN-γ mRNA expression in PBMCs is suppressed by piperine. This compound significantly inhibited the production of these two cytokines by activated PBMCs in a dose-dependent manner. In conclusion, piperine appears to have potential as an immunomodulatory agent for immune system suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Alkaloids / toxicity
  • Benzodioxoles / pharmacology*
  • Benzodioxoles / toxicity
  • Cell Proliferation / drug effects
  • Cytokines / biosynthesis*
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / toxicity
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism*
  • Lymphocyte Activation / immunology
  • Phytohemagglutinins / immunology
  • Piperidines / pharmacology*
  • Piperidines / toxicity
  • Polyunsaturated Alkamides / pharmacology*
  • Polyunsaturated Alkamides / toxicity
  • RNA, Messenger / metabolism


  • Alkaloids
  • Benzodioxoles
  • Cytokines
  • Immunologic Factors
  • Interleukin-2
  • Phytohemagglutinins
  • Piperidines
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Interferon-gamma
  • piperine