Anticytokine Activity and Cytokine-Like Substance Production by Gram-Negative Bacteria Isolated from Patients with Infectious and Inflammatory Postoperative Complications

BACKGROUND: Cytokines play a crucial role in the course and outcome of any infectious and inflammatory process, as they regulate the host immune response of the macroorganism to pathogen invasion. At the same time, it has been established that microorganisms of various species exhibit anticytokine activity (ACA), i.e., the ability to inactivate specific proinflammatory and anti-inflammatory cytokines. Moreover, they are capable of producing cytokine-like substances (CLS). These properties of bacterial pathogens may affect the local cytokine balance in infected tissues and increase the risk of infectious and inflammatory complications.

AIM: The work aimed to characterize the ACA and the ability to produce CLS in gram-negative bacteria isolated from patients with infectious and inflammatory postoperative complications.

MATERIALS AND METHODS: This study included 42 clinical isolates of gram-negative bacteria of various species (Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, C. braakii, Pseudomonas aeruginosa, P. putida, Stenotrophomonas maltophilia) obtained from patients with infectious and inflammatory postoperative complications. Pure bacterial cultures were obtained using standard bacteriological methods, and species identification was performed via direct protein profiling using a MALDI-TOF MS Microflex LT mass spectrometer (Bruker Daltonics, Germany) and MaldiBioTyper 3.0 software. ACA of the bacteria was assessed with respect to interleukin 4 (IL-4), IL-8, IL-1 receptor antagonist (IL-1Ra), and tumor necrosis factor alpha (TNF-α). The production of CLS was evaluated using enzyme-linked immunosorbent assay. ACA and CLS levels were calculated based on the proportion of cytokine inactivation or production relative to control samples and expressed in pg/mL.

RESULTS: Intergeneric, interspecies, and intraspecies/interstrain differences were identified in the prevalence and intensity of ACA against IL-1 receptor antagonist (IL-1Ra), interleukin 4 (IL-4), IL-8, and TNF-α, as well as in the production of CLS corresponding to these cytokines, among clinical isolates of gram-negative microorganisms (representatives of the Enterobacteriaceae family and nonfermenting bacteria) obtained from surgical patients with postoperative infectious and inflammatory complications.

The observed variability in ACA prevalence and intensity, as well as in the ability to produce specific CLS, contributes significantly to the phenotypic diversity—and likely to the pathogenic potential—of causative agents of infectious and inflammatory complications in surgical patients. The clinical isolates of gram-negative bacteria demonstrated the ability to inhibit both anti-inflammatory cytokines (IL-1Ra and IL-4) and proinflammatory immunomodulators (IL-8 and TNF-α), as well as to produce substances with effects similar to those of these regulatory molecules. This diversity in cytokine-associated properties of the pathogens may significantly disrupt cytokine-mediated regulation of inflammation of infectious origin.

CONCLUSION: The results of this study may be used in the future to develop predictive algorithms for assessing the risk of infectious and inflammatory complications following surgical interventions.