Proton-pump inhibitors elevate infection rate in cardiothoracic surgery patients by influencing PMN function in vitro and in vivo

Abstract

Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin. Moreover, IFN-γ feedback mechanisms and signaling by STAT-1 was impaired by PPI. Cardiac surgery is accompanied by developing systemic inflammatory response syndrome with immunosuppressive aspects. We exhibited reduced oxidative burst analyzing cardiac surgery patients' samples receiving or not receiving PPI. Furthermore, a higher rate of infections in patients receiving permanent PPI medication in retrospective analysis was uncovered. Patients undergoing cardiac surgery with cardiopulmonary bypass and regular PPI medication developed significant more infections retrospectively indicating a clinical impact of the immunosuppressive influence of PPI.

Proton-Pump Inhibitors Suppress T Cell Response by Shifting Intracellular Zinc Distribution

“…PPIs are widely and even excessively used in gastrointestinal diseases [ 1 , 2 ]. In recent years, more and more side effects [ 2 , 4 , 8 ], especially a high rate of infection in patients [ 6 , 7 , 8 ], have been reported. PPIs have been suspected to be associated with different infections.…”

“…In addition to CDI, many other infections such as Salmonella , Campylobacter , and community-acquired pneumonia occur but cannot be explained solely by the mechanisms just mentioned. A study from our laboratory also found that PPI treatment increases the risk of infection in patients undergoing cardiac surgery [ 6 ]. We also found that in vitro and in vivo pantoprazole treatment reduces the production of different pro-inflammatory cytokines and the function of polymorphonuclear cells.…”

“…By acting on the final step of gastric acid secretion, these drugs effectively inhibit gastric acid secretion regardless of the presence of other factors. However, more and more side effects have been reported in recent years [ 2 , 4 , 5 ], especially their suppressive effect on the immune system [ 6 , 7 , 8 ]. Meanwhile, in vivo and in vitro experiments have demonstrated that the status of intracellular free zinc has an important regulatory influence on the human immune system [ 9 , 10 , 11 , 12 ].…”

Mortality Risk Factor Stratification in a Retrospective Cohort of Hospitalized Patients with Community Acquired Pneumonia

“…The etiology of the increased in-hospital mortality associated with PPIs remains unclear. However, one study in cardiothoracic patients receiving long-term treatments with PPIs showed reduced oxidative burst as well as small decreases in the killing activity of neutrophils [12]. Moreover, pneumonia developed in signi cantly more patients who were receiving PPIs, which suggests that immunosuppression likely contributed to their increased mortality.…”

Use of gastric-acid suppressants may be a risk factor for enteric peritonitis in patients undergoing peritoneal dialysis: A meta-analysis

“…Third, GASs might impair the function of immune cells against bacterial translocation. Haas and colleagues showed that PPIs have a negative influence on the function of polymorphonuclear cells, including phagocytosis, oxidative burst, chemotaxis and killing activity . Moreover, H 2 RAs might also inhibit the oxidative burst in human neutrophils and disturb the response by dendritic cells to microbial ligands .…”