Neuroendocrine-immune complex as the mirror of the state of exchange of nitrogenous metabolites at rats

Background. Earlier we found that even in intact rats, certain parameters of nitrogenous metabolism fluctuate in a fairly wide range, which further expands in cases of prolonged water loads. Based on this, we have been created three groups that are homogeneous in the parameters of nitrogenous metabolism. We have been shown that each cluster is accompanied by a specific constellation of immune parameters. In this study, an attempt will be made to supplement the immune accompaniment of each constellation of nitrogenous metabolites with parameters of the autonomic nervous and endocrine systems. Material and methods. Experiment was performed on 60 healthy female Wistar rats, both intact and loaded with different mineral waters. Immune status was assessed by thymocytogram, splenocytogram, blood leukocytogram and immunocytogram, as well as by phagocytosis parameters of blood neutrophils and monocytes. The state of autonomous regulation assessed by HRV. The plasma levels of the hormones of adaptation: corticosterone, triiodothyronine and testosterone (by the ELISA) were determined as well as mineralocorticoid, calcitonin and parathyroid activity calculated by their electrolyte markers. Results. 9 neuro-endocrine and 17 immune parameters were identified, the set of which three clusters of nitrogen metabolism clearly differ from each other. The overall accuracy of the classification is 93,3%. Conclusion. The variety of states of exchange of nitrogenous metabolites is accompanied by specific constellations of 26 parameters of neuro-endocrine-immune complex

Varieties of the state of exchange of nitrogenous metabolites (creatinine, urea, uric acid and bilirubin) and their immune accompaniment at rats

Background. Earlier we found that even in intact rats, certain parameters of nitrogenous metabolism and immunity fluctuate in a fairly wide range, which further expands in cases of prolonged water loads. The links between the individual parameters of metabolism and immunity were revealed. Based on this, the aim of this study was to create groups that are homogeneous in the parameters of nitrogenous metabolism, followed by a search for the characteristic parameters of immunity. Material and methods. Experiment was performed on 60 healthy female Wistar rats, both intact and loaded with different mineral waters. The plasma levels and urinary excretion of the nitrogenous metabolites (creatinine, urea, uric acid and bilirubin) were determined. Immune status was assessed by thymocytogram, splenocytogram, blood leukocytogram and immunocytogram, as well as by phagocytosis parameters of blood neutrophils and monocytes. Results. The characteristic features of the members of the most numerous (29 animals) of the first cluster are moderately elevated plasma urea and upper borderline creatinineemia in combination with lower borderline uricemia. In members of the third cluster (22 animals), all seven parameters are in the range of normal. In contrast, rats of the second cluster (n=9) were found to have significantly increased levels of urea and creatinine excretion, as well as uricemia. Each cluster is accompanied by a specific constellation of immune parameters. The overall accuracy of the classification is 95%. Conclusion. The variety of states of exchange of nitrogenous metabolites is accompanied by specific constellations of immune parameters

Immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as in patients with encephalopatia. The purpose of this study is their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 24 men (aged 23-76 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of uric acid, urea and creatinine and parameters of immunity twice (on admission and after 10 days of balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient uricemia exhibits maximal immunotropic activity (R=0,772), followed by creatininemia (R=0,643), urea plasma (R=0,584) and creatinineuria (R=0,506) instead, urea and uric acid excretion correlate with immune parameters insignificantly (R=0,327 and 0,262 respectively). Nitrogenous metabolites together upregulate most parameters of phagocytosis by neutrophils Staph. aureus and E. coli, the level in the blood of CD8 T-lymphocytes, CIC, IgM, componentes of leukocytogram as well as entropy of leukocytogram and immunocytogram. Instead, they downregulate the relative level of lymphocytes in general and of CD4 T-lymphocytes in particular. Conclusion. Nitrogenous metabolites exhibit immunotropic activity in both healthy humans and in patients with chronic pyelonephritis in remission. Both common and distinctive features of immunomodulation were revealed

Role of the lipid peroxidation in immunomodulating effects of the nitrogenous metabolites in rats

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects, but the question of mediators of the immunomodulation remains open. We hypothesized the mediating role of mediators of the autonomic nervous system and adaptation hormones as well as reactive oxygen species. Mediating role in the immunomodulation of neuroendocrine factors is analyzed in a previous article. The aim of this study is to analyze the relationships between the parameters of nitrogenous metabolites and lipid peroxidation as well as between latter and immune parameters subordinate modulations by nitrogenous metabolites. Material and methods. Experiment was performed on 60 healthy female Wistar rats. The plasma level and urinary excretion of the nitrogenous metabolites as well as parameters of lipid peroxidation (diene conjugates, malonic dyaldehid, superoxide dismutase, catalase) and neuroendocrine-immune complex were determined. Results. According to the canonical correlation analysis, the constellation of nitrogenous metabolites determines the state of lipid peroxidation by 38,8%. The latter, in turn, determines the constellation of immune parameters (subject to modulation by nitrogenous metabolites) by 61,4%. On the other hand, the coefficient of determination between nitrogenous metabolites and neuroendocrine parameters is 71,5%, and between the latter and immune status – 89,6%. Taken together, neuroendocrine parameters and lipid peroxidation parameters determine the pool of immune parameters subject to modulation by nitrogenous metabolites by 96,7%. It was previously shown that the coefficient of determination between nitrogenous metabolites and a number of immune parameters is 95,8%. Conclusion. The obtained results, taken together with the previous ones, prove that uric acid, bilirubin, urea and creatinine realize their immunomodulatory effects both directly through receptors of immunocytes (aryl hydrocarbon, adenosine and TL) and with the participation of mediators of autonomic nervous and endocrine systems and lipid peroxidation

Role of autonomous and endocrine factors in immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as patients with dysfunction of neuroendocrine-immune complex, encephalopatia and chronic pyelonephritis. The purpose of this study is clarification of the role of neuro-endocrine factors in their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 17 men (aged 24-70 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of nitrogenous metabolites as well as parameters of immunity and its neuro-endocrine regulation twice (on admission and after balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient, uricosuria exhibits maximal neuro-endocrine activity (R=0,780), followed by bilirubinemia (R=0,742), creatinineuria (R=0,692), uricemia (R=0,636), creatinineemia (R=0,632), urea excretion (R=0,536), instead urea plasma correlate with neuro-endocrine parameters insignificantly (R=0,360). Nitrogenous metabolites together determine the state of neuro-endocrine regulation by 94,2%, which, in turn, determine the state of immunity by 99,9%. Conclusion. Nitrogenous metabolites carry out immunomodulation in different ways: directly through aryl hydrocarbon (bilirubin), toll-like and adenosine (uric acid) receptors of immunocytes; through modulation of the activity of neurons of the autonomous nervous system and endocrinocytes with subsequent neuro-endocrine immunomodulation; and also, apparently, due to an off-receptor effect on neurons, endocrinocytes and immunocytes (urea and creatinine)

Role of the neuroendocrine complex in immunotropic effects of nitrogenous metabolites in rats

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects, both suppressor and enhancing, both in healthy rats and in humans exposed to pathogenic influences. The immunomodulatory effect of bilirubin is probably mediated through aryl hydrocarbon receptors, and uric acid through TL- and adenosine receptors of immune cells. The question of mediators of the immunomodulatory action of urea and creatinine remains open. We hypothesized the mediating role of mediators of the autonomic nervous system and adaptive hormones. The aim of this study is to analyze the relationships between the parameters of nitrogenous metabolites and the parameters of the autonomic nervous and endocrine systems, on the one hand, and between neuroendocrine and immune parameters - on the other hand. Material and methods. Experiment was performed on 60 healthy female Wistar rats. The plasma levels and urinary excretion of the nitrogenous metabolites, HRV and endocrine (corticosterone, triiodothyronine and testosterone plasma levels, calcitonin, parathyroid and mineralocorticoid activities, the thickness of glomerular, fascicular, reticular and medullar zones of adrenals) parameters as well as parameters of immunity were determined. Results. According to the results of canonical correlation analysis, the modulating effects of nitrogenous metabolites on neuroendocrine parameters are quite pronounced and almost identical in terms of bilirubin (R=0,603), creatinine (R=0,602), uric acid (R=0,599) and urea (R=0,586). Taken together, nitrogenous metabolites determine neuroendocrine parameters by 71,5% (R=0,845; χ2(84)=179; p<10-6). Triiodothyronine, fascicular and medullar areas of the adrenal glands, vagal tone and calcitonin activity were the most susceptible to nitrogenous metabolites. In turn, neuroendocrine parameters determine the parameters of immunity, subject to exposure to nitrogenous metabolites, by 95,8% (R=0,979; χ2(264)=405; p<10-6). Conclusion. Previously identified immunomodulatory effects of nitrogenous metabolites are realized, perhaps, through the factors of the autonomic nervous and endocrine systems

Immunotropic effects of nitrogenous metabolites in healthy humans

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects, both in healthy rats and in humans exposed to pathogenic influences. The purpose of this study is their immunotropic activity in clinically healthy people. Materials and Methods. The object of observation were 27 men (aged 24-63 ys) and 14 women (33-62 ys). The plasma levels of the nitrogenous metabolites and parameters of immunity twice with an interval of 5 days was performed. Results. Judging by the multiple correlation coefficient uric acid exhibits maximal immunotropic activity (R=0,665), followed by creatinine (R=0,596) and urea (R=0,541), and closes the constellation of metabolites bilirubin, with the activity of conjugated bilirubin predominating over that of unconjugated (0,539 vs 0,484). Nitrogenous metabolites together upregulate the level in the blood of B-lymphocytes, CIC, IgG, IL-1, eosinophils and monocytes, as well as most parameters of phagocytosis by neutrophils Staph. aureus and E. coli. Instead, they downregulate the phagocytosis activity of Staph. aureus, the relative content of rod-shaped neutrophils, lymphocytes in general and NK-, T active and 0-Lymphocytes in particular. Downregulation of 0-Lymphocytes reflects upregulation of receptor expression, apparently CD22. Conclusion. Nitrogenous metabolites exhibit immunotropic activity in both healthy rats and humans, as well as in patients

Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats

Background. The study of the effect of end products of protein and nucleic acid metabolism on the immune system is of interest not only theoretical but also practical in line with the problems of urotoxins and hemodialysis. In previous studies, we found significant links between uricemia and uricosuria, on the one hand, and immune parameters, on the other hand. In this study, the spectrum of nitrogenous metabolites was expanded due to creatinine, urea and bilirubin. Material and methods. Experiment was performed on 60 healthy female Wistar rats. The plasma level and urinary excretion of the nitrogenous metabolites were determined. Immune status was assessed by thymocytogram, splenocytogram, blood leukocytogram and immunocytogram, as well as phagocytosis of blood neutrophils and monocytes. Results. Both negative and positive metabolic-immune correlations were revealed. Calculation of multiple correlation coefficients between individual metabolite parameters and constellations of immune parameters revealed the maximum immunotropic effect of uricosuria (R=0,637). This is followed by excretion of urea (R=0,617) and creatinine (R=0,606), bilirubinemia (R=0,589), creatinineemia (R=0,567), uricemia (R=0,566) and plasma urea level (R=0,500). The canonical correlation between the constellation of nitrogenous metabolites, on the one hand, and the parameters of immunity, on the other hand, was very strong: R=0,921; χ2(154)=282; p<10-6. Conclusion. Nitrogen metabolites exhibit significant immunotropic activity, both suppressor and enhancing

Immunotropic effects of nitrogenous metabolites (creatinine, urea, uric acid and bilirubin) in humans exposed to the factors of the accident at the Chоrnobyl nuclear power plant

Background. In previous studies, we found that nitrogenous metabolites exhibit significant immunotropic activity, both suppressor and enhancing, at healthy rats. The purpose of this and our subsequent research is to elucidate the links between nitrogenous metabolites and immune parameters in different categories of people, both healthy and sick. Material and methods. The object of observation in 1997 were 19 men and 3 women who were exposed to pathogenic factors of the accident at the Chоrnobyl nuclear power plant during the liquidation of its consequences in 1986-87. The survey was conducted twice - on admission and after two weeks of rehabilitation at the Truskavets’ Spa. The plasma and urinary concentration of the nitrogenous metabolites were determined. Immune status was assessed on tests of I and II levels according to the WHO memorandum. Results. Both negative and positive metabolic-immune correlations were revealed. Calculation of multiple correlation coefficients between individual metabolite parameters and constellations of immune parameters revealed the maximum immunotropic effect of Urea urine (R=0,756). This is followed by Uric acid plasma (R=0,727) and urine (R=0,691), Urea plasma (R=0,622), Creatinine plasma (R=0,588), Bilirubinemia (R=0,546) and Creatinine urine (R=0,510). The canonical correlation between the constellation of nitrogenous metabolites, on the one hand, and the parameters of immunity, on the other hand, was very strong: R=0,971; χ2(15)=239; p<10-5. Conclusion. Nitrogenous metabolites have immunomodulatory effects, both suppressor and enhancing, both in healthy rats and in humans exposed to pathogenic influences

Normal bilirubinemia downregulates the power spectral density of the θ and Δ rhythm, instead upregulates the β rhythm and sympatho-vagal balance in adults humans

Background. Neonatal hyperbilirubinemia has been known to damage neural function. Our goal is to determine whether the neurotropic activity of normal bilirubinemia in adults is evident. Methods. The object of observation were 77 volunteers: 30 women and 47 men aged 49±13 (26 ÷ 76) years without clinical diagnosis. Testing was performed twice with an interval of 4 ÷ 10 days. We determined the plasma levels of the direct and free bilirubin, recorded EEG and HRV followed by analysis of correlations between parameters. Results. Significant downregulating effect of bilirubinemia was found on power spectrum density (PSD) theta and delta rhythm. In contrast, bilirubinemia has an upregulating effect on PSD beta rhythm and sympatho-vagal balance. The canonical correlation between direct & free bilirubin levels, on the one hand, and EEG & HRV parameters, on the other hand, is very strong: R=0,808; R2=0,654; χ2(80)=191; p<10-6 (n=154). A similar canonical correlation was found between individual changes in parameters: R=0,753; R2=0,568; χ2(48)=83; p=0,001 (n=74). Conclusion. Even normal bilirubinemia has an downregulating effect on mainly theta and delta rhythm-generating nuclei and vagal tone, while upregulating effects on sympathetic tone and beta rhythm-generating nuclei