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

Area of Science:

• * Immunology
• * Critical Care Medicine
• * Microbiology

Background:

• * Sepsis and generalized infections are significant risks for critically ill patients.
• * Neutrophil dysfunction is a key factor in infectious complications and sepsis development.
• * Microbial metabolites, particularly aromatic compounds like phenylcarbinol acids (PCA), are hypothesized to cause immunosuppression by inhibiting neutrophil function.

Purpose of the Study:

• * To investigate the relationship between PCA levels and the severity of bacterial infections.
• * To evaluate the impact of PCA on neutrophil phagocytic activity in vitro.

Main Methods:

• * Serum PCA levels were analyzed in patients (n=57) with bacterial infections and healthy donors (n=72) using Gas Chromatography-Flame Ionization Detection (GC-FID).
• * Severity was assessed using APACHE II and SOFA scores.
• * In vitro experiments assessed the effect of clinically relevant PCA concentrations on neutrophil phagocytic activity.

Main Results:

• * PCA levels (including phenylacetic, phenyllactic, hydroxyphenylacetic, and hydroxyphenyllactic acids) were significantly higher in infected patients than in healthy donors, correlating directly with infection severity (APACHE II, SOFA scores).
• * In vitro, PCA compounds (PAA, p-HPAA, PLA) reduced the number of phagocytic neutrophils by an average of 11%.
• * PCA compounds (p-HPAA, PLA, p-HPLA) significantly reduced neutrophil absorption capacity by an average of 26%.

Conclusions:

• * Blood serum levels of phenolcarbonic acids serve as an indicator of bacterial inflammatory process severity.
• * In vitro, PCA at clinically relevant concentrations demonstrably suppresses neutrophil phagocytic activity, contributing to immune suppression in severe infections.