Assessment of Modulating Effect of the Experimental Drug Astrabionorm on Synthesis of Proinflammatory Cytokine IL-1ß and Anti-Inflammatory Cytokine IL-10 in the Splenic Red Pulp Cells in a Mouse Model of Sepsis.

An indirect immunohistochemical method was used to study the production of proinflammatory (IL-1ß) and anti-inflammatory (IL-10) cytokines in the spleen cells of mature male C57BL/6 mice with an experimental model of sepsis and during treatment with a drug based on formic acid aldehyde (Astrabionorm). Clinical isolates of two strains of Pseudomonas aeruginosa were used. In the red pulp of the spleen, interleukin-positive cells represented by mononuclear forms were identified, as well as differences in the intensity of immunohistochemical staining of these cells for the studied interleukins in the two models used. A modulating role of the drug in the production of interleukins by the splenic red pulp cells during sepsis is assumed.

Revisiting the Problem of Finding Effective Sepsis Treatment Solutions.

We studied the effect of a preparation containing ultralow doses of formic aldehyde on the course of experimental sepsis caused by intraperitoneal injection of two different strains of Pseudomonas aeruginosa (1623 and 5266) to C57BL/6 male mice. Microscopy and quantitative bacteriological tests in the dynamics of the infectious process demonstrated a positive effect of the drug: 100% survival of animals, preserved histological structure of the studied organs (lungs, liver, kidneys, spleen, and adrenal glands), a sharp decrease in the level of contamination of the blood and organ homogenates during the first hours after infection, and complete absence of bacteria in inoculates on day 7 after infection. These findings suggest the effectiveness of ultralow doses of formic acid aldehyde in the composition of the medicinal product in the treatment of experimental sepsis caused by P. aeruginosa strains 1623 and 5266 in mice.

Results of Structural and Bacteriological Analysis of the Mouse Adrenal Glands in a Sepsis Model.

The article presents the results of histological and bacteriological analysis of the adrenal glands in two models of sepsis caused by intraperitoneal administration of Pseudomonas aeruginosa strains 1623 and 5266 to sexually mature male C57BL/6 mice. In both models, histological changes in the adrenal glands in the dynamics of sepsis consist in cell destruction and decrease in the absolute areas of the zona glomerulosa, columnar part of the zona fasciculata, and medulla, the development of venous congestion in the absence of pronounced signs of leukocytic infiltration. Most adrenocortical cells of the zona glomerulosa and chromaffin cells of the medulla show signs of destruction. The columnar part of the zona fasciculata loses normal architectonics, the cells undergo degeneration and apoptosis, a significant part of cells in the deep layers of the zona fasciculata remain intact, but do not show tinctorial and ultrastructural signs of steroidogenesis. The active growth of P. aeruginosa colonies from adrenal homogenates in both models already in the first hours after infection of animals makes it possible to associate the revealed structural changes in the adrenal glands with the direct negative effect of P. aeruginosa, and high levels of mRNA of proinflammatory cytokines in the adrenal tissues raise the question of the possible synthesis of these modulators of inflammation in the adrenal parenchyma of septic animals.

Comparative Characteristics of the Spleen White Pulp in Experimental Models of Sepsis Caused by Different Strains of Pseudomonas aeruginosa.

We describe reactive changes in the spleen white pulp in male C57BL/6 mice with experimental sepsis induced by intraperitoneal administration of Pseudomonas aeruginosa 1840 (Pa1840) with exotoxin U gene or Pseudomonas aeruginosa 1623 (Pa1623) with exotoxin S gene. Histological analysis and morphometry revealed hypoplasia of the spleen white pulp in mice with sepsis induced by Pa1840, while sepsis caused by Pa1623 was associated with its hyperplasia; with apoptosis of white pulp cells was observed in both cases. The results attest to ambiguous nature of the reactive changes in the white pulp of the spleen in experimental sepsis models initiated by Pa1840 and Pa1623 stains.