[PARTICIPATION OF AROMATIC MICROBIAL METABOLITES IN THE DEVELOPMENT OF SEVERE INFECTION AND SEPSIS.]

Background Actuality of the problem of infection in critically ill patients remains high. Addition a local infectious processes have a tendency to rapid generalization and sepsis. Neutrophilsfunction failure plays a key role in the patho- genesis of infectious complications and sepsis. The hypothesis about the role of microbial metabolites in the formation of immunosuppression, in particular in the inhibition of phagocytic activity of neutrophils as the first line of defense against bacteria is acquiring more and more supporters. Among the microbial metabolites aromatic compounds, such as phenylcarbinol acid (PCA) are of particular interest. Their concentration in the blood reaches a maximum in case of generalized infection, and correlates with mortality in patients in critical conditions, and PCA biological activity confirmed by earlier researches in vitro. The purpose of the study was to reveal the relationship of the PCA with the severity of bacterial infections and to assess the effect of PCA on neutrophils phagocytic activity.

Materials and methods: At the first stage the levels of PCA (GCh-FID method) in the serum ofpatients (n=57) with a documented bacterial infection of varying severity, confirmed APACHE II and SOFA scales were analyzed comparing with healthy donors (n=72). During the second stage the effect of clinically-relevant concentrations of PCA on neutrophils phagocytic activity ofperipheral blood was analyzed in vitro.

Results: The levels ofphenylacetic (PAA), phenyllactic (PLA), hydroxyphenylacetic (p-HPAA) and hydroxyphenyllactic (p-HPLA) acids in patients were significantly higher than in healthy donors, reaching the highest values in severe infection. High direct correlation of PCA levels with the indicators ofscales APACHE II and SOFA was detected. A significant decrease in the number ofphagocytic neutrophils under the influence PAA, p-HPAA and PLA was identified in vitro experiment on average 11%. The most significant influence p-HPAA, PLA and p-HPLA have made on the intensity of the neutrophils absorption capacity reducing this parameter by an average of 26%. Also noted that phenylpropionic acid (PPC) which is in blood of healthy donors, disappears in critical ill patients.

Conclusion: Phenolcarbonic acids level in the blood serum shows the severity of bacterial inflammatory process. Ex- periment in vitro shows that the PCA in clinically-relevant concentrations is able to suppress the neutrophilsphagocytic activity.