Systematic Review

The Use of Proton Pump Inhibitors and Increased Susceptibility to Enteric Infection

C. Bavishi; H. L. DuPont

Disclosures

Aliment Pharmacol Ther. 2011;34(11):1269-1281. 

In This Article

Anti-inflammatory Effects of PPI Use

In vitro studies involving various PPIs have shown a wide range of immunomodulatory and anti-inflammatory effects. In vitro studies have shown that omeprazole exerts significant anti-oxidant effects against HOCl- and iron- and copper-driven oxidant damage.[32] Pantoprazole, omeprazole and lansoprazole showed hydroxyl ion scavenger activity at higher concentrations.[33] Among the inflammatory cells, neutrophils are particularly susceptible to PPI therapy, resulting in inhibition of neutrophil's bactericidal activity.[34–36]

As with non-enteric infectious diseases, inflammatory response against gastrointestinal pathogens is regulated by complex multi-step processes involving microbial products, chemo-attractants, cytokines and interleukins, adhesion molecules and leucocytes.

Proton pump inhibitors have been shown to affect: chemotactic migration of neutrophils in response to formyl-MLP (formyl-methionyl-leucyl-phenylalanine), a potent chemo-attractant in bacteria;[36,37] phagocytosis of microorganisms;[38] and neutrophil-endothelium expression of adhesion molecules.[39] These important negative effects of PPIs on neutrophil's function may relate to alteration of v-type of H+ ATPases on neutrophils,[40] inhibition of IL-8 derived immune response or inhibition of formyl-MLP-induced elevation of the cytosolic calcium concentration in polymorphonuclear neutrophils.[41]

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