The dissertation presents a theoretical integration and solution to a topical scientific problem, a pathogenetic rationale for the use of glucosaminylmuramyl dipeptide for the prevention of chronic inflammation. The model of secondary chronic inflammation demonstrated that, by the findings obtained for the basic inflammation parameter of blood system reactions, the use of glucosaminylmuramyl dipeptide significantly reduces the chronicity of inflammation. At inflammation against the background of glucosaminylmuramyl dipeptide administration, in the monitoring period at the day 2, the changes were registered which are more similar to those at the day 3 of the monitoring period with the usual course of inflammation: decreased neutrophil count and focal thinning of cellular density in the central areas of inflammatory infiltrate in layers of loose fibrous in the process of disorganization of connective tissue between bundles of muscle fibers. Study of the cell composition in the center of the inflammation site reveals a significant anti-inflammatory effect of glucosaminylmuramyl dipeptide under conditions of carrageenan inflammation. This effect is registered by the various components of the cell-tissue reaction of the inflammation site: leukocyte infiltration, proliferation of connective tissue elements. Infiltration of the inflammatory tissue with granulocytes remains. Other leukocyte infiltration increases at different periods of inflammation and decreases at later periods. The use of glucosaminylmuramyl dipeptide affects the content of various cell elements typical of the inflammatory response, and the cell composition changes at the periphery of carrageenan inflammation site are identical with those in the center, but less pronounced. During the inflammation caused by the use of glucosaminylmuramyl dipeptide, compared to the natural course of the process, the total number of karyocytes was significantly 2.1-fold higher, p<0.01 at 6 h, and significantly lower at days 5 and 21 (respectively, 2.4-fold, p<0.001 and 1.41-fold, p<0.05). During the inflammation caused by the use of glucosaminylmuramyl dipeptide, the total number of karyocytes in the early periods is slightly higher, and in later terms is significantly lower than during the natural course of the process. The number of blast cells in the early stages of inflammation caused by the administered glucosaminylmuramyl dipeptide is higher, and in later is lower than during the natural course of inflammation. A significantly increased number of immature neutrophils at the 6th hour and the day 14 (1.6-fold, p<0.05, and 2.2-fold, p<0.05, respectively), significantly decreased counts of immature neutrophils at the days 1, 5 (2.4-fold, p<0.05 and 2.2-fold, p<0.01, respectively) are seen. The lagging number of cells at the days 1 and 5 indicates their more intensive peripheralization from the bone marrow into the blood, and those rest from the days 21 to 28 give an evidence of a less intensive hematopoiesis during the inflammation chronization due to the decreased chronicity. There is a shift of the peak from the day 21 to the 14, that, as for the blast cells as well, reflects earlier activation of hematopoiesis. At inflammation against the use of glucosaminylmuramyl dipeptide compared with its natural course, the content of monocytes was significantly higher on the day 14 and less on the day 5 (2.3-fold, p<0.001 and 2.13-fold, p<0.001, respectively). During inflammation against the use of glucosaminylmuramyl dipeptide compared to the natural course, activation of monocytopoiesis is more pronounced in the early periods and less in the later periods. It is connected with decreased chronicity of inflammation. Lymphocyte content is significantly higher at 6 hours, days 2 and 14 (1.93-fold, p<0.05, 2.33-fold, p<0.05, and 1.53 fold, p<0.05, respectively) and lower at the days 5, 21 (2.2-fold, p<0.001, 1.3-fold, p<0.05, respectively). The lymphocyte content is greater within the first 14 days of inflammation and less at later periods corresponding to the chronicity period of inflammation. Activation of lymphopoiesis in this case is greater than during the natural course of inflammation, and in the period of chronicity of the process it is less, that indicates a decreased chronicity. During inflammation against the use of glucosaminylmuramyl dipeptide, compared to the natural course of the process, in the early stages of inflammation, a greater number of leukocytes emigrate to the lesion, compared to more distant terms. The use of glucosaminylmuramyl dipeptide leads to decreased chronicity of inflammation due to greater activation of hematopoiesis, and, consequently, the entry of leukocytes into the blood and inflammation site in the early stages of inflammation. During inflammation against the use of glucosaminylmuramyl dipeptide, unlike the natural course of inflammation, decreased total number of leukocytes is observed at the days 5 and 14 that is associated with increased release of leukocytes into the inflammation site. Compared to the natural course of inflammation, there is a significant decrease in the number of monocytes at the days 1 and 5 (2.17-fold, p<0.001, and 1.8-fold, p<0.05, respectively), that corresponds to the dynamics of the total number of leukocytes and the content of granulocytes; it evidences that the use of glucosaminylmuramyl dipeptide reduces the chronicity of inflammation. At the natural course of inflammation, according to the number of lymphocytes in the blood, its significant decrease compared with the control at the 6th hour, and also a significant increase at the days 2, 5 and 14 are observed. Compared to the natural course of inflammation, it is significantly less by the day 5, 1.81-fold, p<0,05. These data concerning the course and tend of inflammation are similar to those for monocytes, and indicate that the use of glucosaminylmuramyl dipeptide reduces the intensity of chronic inflammation. Compared with the natural course of inflammation, the concentration of TNF alpha in blood during inflammation against the background of glucosaminylmuramyl dipeptide administration, is significantly higher within the time from the 6th hour to the day 3. At the days 5-7 a decreased concentration of TNF alpha against the background of the use of glucosaminylmuramyl dipeptide compared to the natural course of inflammation is seen. From the day 10 to 28 there was a significant decrease in TNF alpha concentration against the background of glucosaminylmuramyl dipeptide administration. Compared to the natural course of inflammation, the IL-2 blood concentration during inflammation against the background of the use of glucosaminylmuramyl dipeptide was significantly 1.11 times reduced at 6th hour (p<0.05). From the day 1 to day 3, the concentration of IL-2 in blood against the background of the use of glucosaminylmuramyl dipeptide was significantly higher compared to the usual course of inflammation. From the day 5 to 7 decreased concentrations of IL-2 in blood against the use of glucosaminylmuramyl dipeptide, 1.19-fold (p<0.001); 1.26-fold (p<0.001), respectively, were registered. At the days 10 and 14, the IL-2 blood concentration against the use of glucosaminylmuramyl dipeptide showed no difference with the natural course of inflammation. At the days 21 and 28, we registered a significant decrease in the IL-2 blood concentration against the use of glucosaminylmuramyl dipeptide, respectively 2.91-fold (p<0.001) and 1.59-fold (p<0.001), compared with the natural course of inflammation. Compared to the natural course of inflammation, the IL-2 concentrations in the peripheral blood during inflammation with the use of glucosaminylmuramyl dipeptide at the 6th hour and the day 1 were significantly higher, 1.42-fold (p<0.001); 1.35-fold (p<0.001), respectively. From the day 3 to the day 21 we observe a 1.43-fold increase in the IL-10 concentration in the peripheral blood during inflammation against the background of glucosaminylmuramyl dipeptide administration compared to the natural course of inflammation, respectively. At the day 28 during inflammation against the background of administration of glucosaminylmuramyl dipeptide, the concentration of IL-10 was registered to be 1.04-fold (p<0.001) reduced compared to the natural course of inflammation, indicating decreased chronicity of inflammation.
