:From the viewpoint of the general pathology, most of the human diseases are associated with a limited number of pathogenic processes such as inflammation, tumor growth, thrombosis, necrosis, fibrosis, atrophy, pathological hypertrophy, dysplasia and metaplasia. The phenomenon of chronic low-grade inflammation could be attributed to non-classical forms of inflammation, which include many neurodegenerative processes, pathological variants of insulin resistance, atherosclerosis, and other manifestations of the endothelial dysfunction. Individual and universal manifestations of cellular stress could be considered as a basic element of all these pathologies, which has both physiological and pathophysiological significance.:The review examines the causes, main phenomena, developmental directions and outcomes of cellular stress using a phylogenetically conservative set of genes and their activation pathways, as well as tissue stress and its role in inflammatory and para-inflammatory processes.:The main ways towards the realization of cellular stress and its functional blocks were outlined. The main stages of tissue stress and the classification of its typical manifestations, as well as its participation in the development of the classical and non-classical variants of the inflammatory process, were also described.:The mechanisms of cellular and tissue stress are structured into the complex systems, which include networks that enable the exchange of information with multidirectional signaling pathways which together make these systems internally contradictory, and the result of their effects is often unpredictable. However, the possible solutions require new theoretical and methodological approaches, one of which includes the transition to integral criteria, which plausibly reflect the holistic image of these processes.

Currently, the most significant mediators of the systemic inflammatory response (SIR), specific to the development of critical states in sepsis, have the chaotic changes of concentrations in the blood. The solution to the problem is using integral indicators. A scoring scale of the SIR (0-16 points) is proposed based on the determination in the blood plasma of CRP, TNF-α, IL-6, IL-8 and IL-10. The scale was used in the survey of 167 patients with a diagnosis of sepsis (43 patients with sepsis according to definitions of "Sepsis-1 or 2" and 124 patients with sepsis according to the criteria of "Sepsis-3"); septic shock was verified in 31 cases and in 48 cases lethal outcomes were recorded. The association of SIR with critical complications of sepsis was revealed, especially under acute septic shock and in cases of a "second wave" (days 5-7) of critical complications. In contrast, prolonged/ subacute sepsis (more than 14 days) under tertiary peritonitis is characterised by a lesser dependence of the criticality of the state on the severity of SIR. The proposed scale is an open system and allows you to modify the range of used particular indicators that are compatible by pathogenetic and diagnostic significance.

The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

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