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Proton pump inhibitors exert anti-inflammatory effects and decrease human microglial and monocytic THP-1 cell

Sadayuki Hashioka1, Andis Klegeris, Patrick L McGeer

  • 1Department of Psychiatry, Kinsmen Laboratory of Neurological Research, The University of British Columbia, Vancouver, BC, Canada.

Experimental Neurology
|February 24, 2009
PubMed

Insights

Proton pump inhibitors (PPIs) demonstrate anti-inflammatory effects, reducing neurotoxicity from activated microglia. Combining PPIs with NSAIDs may offer new treatments for neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglia activation contributes to neuroinflammation and neurotoxicity in neurodegenerative diseases.
  • Proton pump inhibitors (PPIs) are commonly used for acid-related disorders.
  • The potential anti-inflammatory effects of PPIs on microglia remain largely unexplored.

Purpose of the Study:

  • To investigate the anti-inflammatory properties of lansoprazole (LPZ) and omeprazole (OPZ) on microglia.
  • To assess the impact of PPIs on microglial-induced neurotoxicity.
  • To evaluate the combined effects of PPIs and NSAIDs on neuroinflammation.

Main Methods:

  • Assessing the neurotoxic effects of stimulated microglia and THP-1 cell supernatants on SH-SY5Y neuroblastoma cells.
  • Measuring pro-inflammatory cytokine (TNF-alpha and IL-6) production using enzyme-linked immunosorbent assays (ELISAs).
  • Investigating the synergistic effects of PPIs with S-ibuprofen (IBP), a non-steroidal anti-inflammatory drug (NSAID).

Main Results:

  • Both LPZ and OPZ exhibited protective effects against microglial supernatant-induced neurotoxicity.
  • A synergistic neuroprotective effect was observed when PPIs were combined with S-ibuprofen.
  • PPIs significantly reduced TNF-alpha secretion from stimulated THP-1 cells in a dose-dependent manner, with a trend towards reduced IL-6.

Conclusions:

  • Proton pump inhibitors possess significant anti-inflammatory effects on microglia and monocytes.
  • PPIs can mitigate microglial and monocytic neurotoxicity.
  • Combination therapy with PPIs and NSAIDs shows promise for treating neurodegenerative diseases linked to microglial activation.

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