NIV Congres

Introduction: Adenosine exerts anti-inflammatory and tissue protective effects during systemic inflammation. While the anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance, the direct tissue protective effects might limit organ damage.

Aim of the study: To investigate the effects of a common loss-of-function variant of the Adenosine Monophosphate Deaminase 1 gene (AMPD1), which is associated with increased adenosine formation, in patients with sepsis.

Materials and Methods: In a prospective cohort, genetic-association study, the effects of the presence of the AMPD1 gene on immune function, multi-organ dysfunction and mortality in septic patients was studied. Pneumosepsis patients (n = 402) and controls without infection (n = 101) were enrolled.

Results: In pneumosepsis patients and controls, the prevalence of the 34C>T (rs17602729) mutation in the AMPD1 gene was similar. Univariate logistic regression analysis showed a tendency of increased mortality in patients with the CT genotype, compared to patients with the CC genotype (OR 1.53; 95% CI 0.95-2.5). Moreover, carriers of the CT genotype tended to suffer more from multi-organ dysfunction, OR 1.4 (0.84-2.3) and 3.0 (0.66-13.8), for CT and TT, respectively (p = 0.07). In septic carriers of the CT genotype, the ex vivo production of TNF-α by LPS-stimulated monocytes was attenuated (p = 0.005), indicative for more pronounced immunoparalysis in these patients.

Conclusion: The presence the 34C>T variant of the AMPD1 gene is not related to infection susceptibility, however it is associated with more pronounced immunoparalysis in patients with sepsis, and shows a tendency towards increased mortality. Mechanistically, the anti-inflammatory effects of adenosine may account for this and apparently overrule its direct tissue protective effects.