<p>The modern view of systemic inflammatory response revolves around the fact that the key pathophysiological link is immunosuppression rather than the initial hyperinflammatory phase as previously supposed. Immunosuppression in critically induced systemic inflammatory response syndrome is associated with increased susceptibility of patients to secondary nosocomial infections and increased probability of progression to multiple organ failure. The role of programmed cell death protein 1 (PD-1) has been investigated in the context of systemic inflammatory response from the standpoint of its participation in the development of immunosuppression. One of the mechanisms of immunosuppression is the exhaustion of T-cells mediated by inhibitory PD-1 receptors. In the body, the PD-1/programmed death-ligand 1 (PD-L1) pathway regulates autoimmunity, tumour immunity, transplant immunity, allergies and immunopathology. This review summarises the results of experimental studies demonstrating that blocking the interaction of PD-1 with its PD-L1 ligand recovers T-cell dysfunction and improves survival rates in animal models of sepsis. Moreover, a clinical case of the use of anti-PD-1 therapy that led to improvement in the status of a critically ill patient is described. Undesirable side effects of this therapeutic approach are also evaluated. Meanwhile, immune checkpoint inhibitors have been introduced into clinical practice to treat certain forms of cancer. Increased expression of PD-1 receptors in systemic inflammatory response syndrome is may thus be a prognostic marker.</p><p>Received 2 August 2019. Revised 15 November 2019. Accepted 15 November 2019.</p><p><strong>Funding:</strong> The work is supported by a grant of the President of the Russian Federation for leading scientific schools НШ-2696.2018.7 “Prediction and preventive intensive care of persistent multiple organ failure.”</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p>

Tissue engineering is a promising area for the production of small-diameter vascular grafts. In recent years, a number of strategies have been developed to make the polymer surfaces of vascular prostheses capable to selectively adhesion of endothelial cells. The arginine–glycine–aspartic acid (RGD) sequence (a cell adhesion site that is present on many extracellular matrix proteins) is the promising target for modification. The efficiency of attachment of endothelial cells can be influenced both by the structure of RGD peptide and the extent of linker group.Aim: to determine the optimal method for modification of non-woven matrices of polyhydroxybutyrate/ valerate and polycaprolactone (PHBV/PCL) by RGD-peptides leading to the increasing of adhesion, viability and proliferation of endothelial cells.Materials and methods. Electrospinning was used to produce 4 mm diameter tubular polymer matrices from PHBV/PCL. Modification of surface of polymer scaffolds was performed using 4,7,10-trioxa-1,13-tridekandiamin, hexamethylenediamine, glutaraldehyde, ninhydrin, ascorbic acid, a cyclic peptide c [RGDFK], RGDK, AhRGD. The quality of modification was assessed by ninhydrin test and determination of arginine-containing peptide. The structure of the surface of matrices before and after modification was studied by scanning electron microscopy. Adhesion, viability and proliferation of Human umbilical vein (HUVEC) endothelial cells cultured for 7 days on the surface of matrices in the presence of RGD and without one were examined using fluorescence and laser scanning microscopy after the cells were pre-stained with fluorescent nuclear dyes (ethidium bromide and Hoechst 33342), and also by special kits for proliferation assessment (Click-iTTM Plus EdU Alexa FluorTM 488 Imaging Kit).Results. RGD peptides bound to the matrix surface via a long linker (4,7,10-trioxa-1,13-tridecanediamine) were characterized by the increased bioavailability and activity. High level of cell adhesion, viability and proliferation were noted on the surface of RGDK and c[RGDFK] modified matrices, whereas their paired analogues with a short linker (hexamethylenediamine) showed low results of cellular viability even against satisfactory cell adhesion.Discussion. Non-woven matrices based on PHBV/PCL and modified using 4,7,10-trioxa-1,13-tridecanediamine showed better results in case of adhesion of HUVEC and subsequent preservation of cell viability and proliferation. RGD-containing peptides of RGDK and c [RGDFK] were more tropic to endothelial cell receptors.

The immune system in critical illnesses initiates local inflammation in the damaged area. In the absence of a balance between local and systemic inflammations, an infectious or non-infectious systemic inflammatory response follows, which has a stage of "hyper inflammation - compensatory anti-inflammatory response", that may result in multi-organ failure. The final stage of critical ill-nesses, therefore, will be characterized by induced immunosuppression with the impaired function of neutrophils, monocytes, macrophages and dendritic cells and release of myeloid-derived suppres-sor cells. The aim of the review is to evaluate the contribution of various components of the im-mune response to the formation of induced immune suppression from the perspective of candidate diagnostic markers.

Background We fabricated biodegradable, bioactive scaffolds to guide the differentiation of endothelial progenitor cells. Aim To study in vitro activity of the bioactive factors incorporated into the poly (3-hydroxubutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) scaffolds. Methods Nonwoven scaffolds were blended of PHBV and PCL utilizing either separate or combined incorporation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1α (SDF-1α) by emulsion electrospinning. We further studied adhesion, viability, and proliferation of EA.hy 926 endothelial cells cultured on these scaffolds and evaluated vasculogenesis, cell index, and secretory profile in response to the addition of abovementioned bioactive factors. Results We showed that VEGF, bFGF, and SDF-1α retain their bioactivity upon the incorporation into the PHBV/PCL scaffolds. Scaffolds with all three bioactive factors incorporated demonstrated superior performance in comparison with those containing any of these factors alone. Diffusion of the bioactive factors into the culture medium stimulated the secretion of interleukin-10, and VE-cadherin by endothelial cells that indicated anti-inflammatory response and tight intercellular junctions. We also detected the low level of secreted VEGF-A from the scaffolds with VEGF suggestive of its physiological regulation. Conclusion Bioactive factors retain their bioactivity upon the incorporation into the PHBV/ PCL scaffolds. Combination of VEGF, bFGF, and SDF-1a improves cellular response compared to the incorporation of any of these factors alone.

The maladaptive nature of the systemic inflammatory response syndrome, which may be caused by sepsis, trauma, or ischemia-reperfusion injury, is characterized by a shift towards the distant effects of pro-and anti-inflammatory mediators. Shock, blood loss, and metabolic disorders may cause the onset of multiple organ dysfunction syndrome. The final phase of critical illness is generally associated with induced immunosuppression and dysfunctions of neutrophils, monocytes and macrophages, dendritic cells, release of myeloid-derived suppressor cells, damage to glycocalyx and endothelium, and impaired metabolic conjugation. This review is aimed at providing novel evidences on the roles of various immune components, either innate or acquired, in the induction of immunosuppression from the standpoint of the rapid diagnosis of immune disorders in the intensive care unit using flow cytometry as a commonly accepted option.