ENDOGENOUS INTOXICATION AND INFLAMMATION: REACTION SEQUENCE AND INFORMATIVITY OF THE MARKERS (review)

Abstract

Abstract According to modern phylogenetic theory of general pathology (V.N. Titov, 2003, 2013) inflammation is a nonspecific biological reaction, providing the removal of excessive amount of high-molecular macromolecules and maintenance of metabolic homeostasis (endoecology). The increase of any metabolite concentration above the physiological range is a violation of the «purity» of inter-cellular medium. This triggers two nonspecific biological reactions, namely the excretion used to re-move «biological waste» of a molecular weight less than 70 kD and the inflammation in case the lar-ger molecules and their complexes should be removed via neutrophils, resident macrophages and en-dothelial cells. Blood concentration of leukocytes has been used for evaluation of inflammation and intoxication activity for many decades. However, at the molecular level there is a requirement in precise differentiation of metabolites, activating leukocytes, and metabolites, excessively forming as a result of activation, because the last disturb molecular homeostasis and may damage cells and tissues. Validity of leucocytal intoxication index (LII) of Ya.Ya. Kalf-Kalif, concentration ratio of low and medium molecular weight substances, average molecular peptides, total and effective albumin as markers of endogenous intoxication (M.Ya. Malakhova, 2005) are considered. It is shown that pri-mary agent, activating neutrophils and some factors of humoral immunity, is a lipopolysaccharide (endotoxin) of gram-negative microflora (M.Yu. Yakovlev, 2003; O.W. McIntyre, 2011). An excess of endotoxin inflow is possible under intestine and liver pathologies, and due to sympathoadrenal system activation, and also with feed and air. The overload of systems and organs of elimination of endotoxin causes secondary immunodeficiency, which becomes the cause of acute and chronic in-flammatory processes of various localizations. It is offered to consider lipopolysaccharide of gram-negative microflora as a primary agent of endogenous intoxication and all the metabolites, produces at increased concentrations as a result of polymorphonuclear leukocytes activation such as reactive oxygen species, oxidated proteins, products of lipid peroxidation and proteolysis, as a secondary one. Such an approach allows to single out various points of application for therapy of endogenous intoxi-cation: i) elimination of excessive concentration of lipopolysaccharide in blood by limiting its pro-duction and income from internal and external sources, as well as by a variety of methods of active binding and excretion of endotoxin (S.V. Smirnov et al., 2003; K. Battenschoen et al., 2010); ii) re-ducing the concentration of «secondary» metabolites in blood and tissues. Keywords: endogenous intoxication, segmentated neutrophils, lipopolysaсcharides, inflamma-tion, endotoxinemia, endoecology.