Regulation of anti-cytokine activity of bacterial isolates in post-surgical complications by synthetic peptide ZP2

The ZP2 peptide is a synthetic analogue of active center in granulocyte-macrophage colony stimulating factor (GM-CSF). It exerts a wide range of immunobiological effects, including antibacterial activity. However, its effect (at sub-inhibitory concentrations) on the biology of Gram-negative bacteria remains poorly understood. The aim of this study was to compare the effect of the synthetic peptide ZP2 on the anti-cytokine activity (ACA) of Gram-negative bacteria isolated during infectious complications post-surgery. The study included 42 clinical isolates of Gram-negative bacteria of various species (Escherichia coli, Klebsiella pneumoniae, Citrobacter braakii, C. freundii, Stenotrophamonas maltophilia, Pseudomonas aeruginosa, P. putida) obtained from patients with post-surgical complications. The microorganisms were grown in meat-peptone broth (BCH) with synthetic peptide ZP2 at 37°C for 24 hours. ACA against IL-4, IL-8, IL-1Rа and TNFα was determined by enzyme immunoassay (ELISA). To evaluate ACA, the proportion of cytokine inactivation in the experiment relative to controls was calculated and expressed as pg/ml. The in vitro experiments were conducted to assess the ability to inactivate some pro- and anti-inflammatory cytokines (IL-4, IL-8, IL-1Rа, TNFα) by different bacterial isolates, thus demonstrating a genus/species dependence of these effects. It was shown that the synthetic ZP2 peptide was characterized by an inhibitory and indifferent effect on the ability of clinical strains of microorganisms to inactivate the studied pro- and anti-inflammatory cytokines. It has been established that ZP2 has a modifying potential that can change both incidence and grade of the ACA of Gram-negative bacteria isolates obtained at post-surgical complications. Gram-negative bacteria isolated during postoperative complications are capable of secreting compounds that inactivate cytokines IL-4, IL-8, IL-1Ra, TNFa. Synthetic peptide ZP2 at sub-inhibitory concentrations exerts a modifying effect on manifestations of anticytokine activity by the studied microorganisms. The revealed in vitro modifying effects of synthetic peptide ZP2 expand the range of its potential clinical applications.