P2X7 receptor polymorphism impairs extracellular adenosine 5'-triphosphate-induced interleukin-18 release from human monocytes

Genes Immun. 2004 Nov;5(7):588-91. doi: 10.1038/sj.gene.6364127.


Interleukin (IL)-18 is an important proinflammatory cytokine processed and released from cells of the monocyte lineage by activation of the P2X(7) receptor by extracellular adenosine 5'-triphosphate (ATP). We examined if a loss-of-function polymorphism of the human P2X(7) receptor (glutamic acid-496 to alanine) impairs this process. Using a whole blood-based assay, ATP-induced release of IL-18 from homozygous subjects after 120 min incubation with ATP was 42% of that from wild-type subjects. Moreover, the level of ATP-induced IL-18 release from lipopolysaccharide (LPS)-primed monocytes of homozygous subjects after 30 and 60 min incubation with ATP was 21 and 44%, respectively, of that from wild-type monocytes. Nigericin, a K(+) ionophore, induced a similar release of IL-18 from monocytes of either genotype. ATP-induced ethidium(+) uptake in LPS-primed, monocytes of homozygous subjects was only 11% of that in wild-type monocytes, while P2X(7) surface expression on LPS-primed, homozygous monocytes was 44% of that on wild-type monocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism*
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Polymorphism, Genetic / genetics*
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2X7


  • Interleukin-18
  • P2RX7 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate