Does stress-induced release of interleukin-1 cause liver injury?

It is well established that repeated immobilization stress (RIS) is induced by increased levels of cytokines and the emergence of lesions in the liver. Our data prove that interleukin-1 (IL-1) causes liver lesions in stressed Wistar rats. In essence, the relationship between IL-1 and stress-induced liver injury is based on three findings: (1) IL-1β treatment causes liver inflammation, consisting of infiltrating monocytes and the appearance of necrosis by increasing lipid peroxidation and protein carbonylation.

[Immunosupressive effect of hypokinetic stress and sensitization of thymus to glucocorticoids].

24-hour hypokinetic stress expressed in decrease of sensitivity of cellular and humoral immu nity to subsequent immunization with sheep erythrocytes was studied. The development of this phenomenon is associated with sensitization of lymphoid tissue to hypoplasia effect of glycocorticoid hormones. In introduction of glycocorticoid stress, the animals revealed a more pronounced depression of proliferative activity of thymocytes compared with non stressed animals.

[Influence repeated stress on immune responciveness and monooxigenase activity of normotensive and hypertensive rats].

Repeated stress led to antipodal directions in immune system and cytochrome P450 activities of normotensive and hypertensive rats. Enhancement of the Reaction of Delayed Hypersensitivity, suppression of cytochrome P450-mediated monooxigenase activities were observed in Wistar rats. On the contrary, in the NISAG decrease of the Reaction Delayed Hypersensitivity, elevation of cytochrome P450-mediated monooxigenase activities were observed, as comparison with Wistar rats.

[The effect of recombinant interleukin 1beta on cytochrome P-450 dependent monooxygenases in rat liver and kidney].

Effects of a single administration of the human recombinant interleukin 1beta (rIL-1beta, betaleukin) on the cytochrome P-450 dependent monooxygenase activity in rat liver and kidney were evaluated in intact rats and on the background of cytochrome P-450 inductors. It was found that betaleukin suppressed the CYP1A1/2-dependent ethoxyresorufin-o-deethylase activity in both liver and kidney, as well as the CYP2C-dependent dibenzylfluorescein-debenzylase and CYP2E1-dependent nitrophenol-hydroxylase activity in liver, but induced CYP3A-dependent N-demethylation of erythromycin in liver and kidney. Betaleukin also inhibited the beta-naphthoflavone-induced monooxygenase activity in liver, while only insignificantly acted upon the induced monooxygenases in kidney.

[The effect of ladasten on the activation-induced expression of Fas receptor on T-lymphocytes and their sensitivity to Fas-induced apoptosis].

The effects of ladasten on the activation-induced expression of Fas-receptor on T-lymphocytes, their sensitivity to Fas-induced apoptosis, and the expression of mitogen-activated ERKI/ERK2 protein kinases have been studied. In the range of concentrations 0.1-10 microM, ladasten exhibited a comitogenic effect on the TCR-mediated stimulation of T-lymhocytes ion the peripheral human blood, which was accompanied by an increase in the level of phosphorylated form of ERK-2.

[Insertional polymorphism of the CYP2E1 gene in infiltrative pulmonary tuberculosis in populations of Bashkortostan Republic].

Insertion polymorphism Ins96 of the CYP2E1 promoter region was for the first time studied in three ethnic groups of Bashkortostan. Population-specific features of genotype and allele frequency distributions were observed. The CYP2E1 polymorphism was associated with infiltrative pulmonary tuberculosis in the Bashkortostan population.

[Effect of ladasten on proliferative activity and apoptosis in peripheral blood T-lymphocytes ].

The effects of ladasten (0.1-10 microM) on the proliferative activity, apoptosis, and expression of the apoptosis protein regulators (bcl-2 and p53) was studied in 72-h cultures of T-lymphocytes of human peripheral blood activated by anti-CD3MCA. In the concentration interval from 0.

[Polymorphism of the tumor necrosis factor alpha gene in patients with infiltrative tuberculosis and from the Bashkorstan populations].

The polymorphism at position -308 of the TNF-alpha gene promoter was analyzed in three ethnic groups and in patients with infiltrative pulmonary tuberculosis from Bashkortostan. No interethnic difference in allele or genotype frequency distribution was observed. The frequency of allele TNF2 in tuberculosis patients was significantly higher than in controls (chi 2 = 11.

[Effect of bemethyl on cytochrome P-450-dependent monoxygenases in the human liver and lymphocytes].

Effects of the actoprotector bemithyl (50 mg/kg, p.o.) upon a single or five-fold administration on the cytochrome P-450 and b5 content and the isoform-specific and nonspecific monooxygenase activity [aminopyrine-N-demethylase, aniline-p-hydroxylase, 4-nitroanisole-o-demethylase,2,5-diphenyloxazole-p-hydroxylase, 7-ethoxyresorufin-o-deethylase (EROD), benzyloxyresorufin-o-debenzylase (BROD)] in rat liver were evaluated.

[Phenomenon of apoptosis in the survival of enterobacteria in the parasite-host system].

Data on the apoptosis phenomenon with enterobacteria used as a model are presented. One of the mechanisms regulating the vital activity of eukaryotic cells is, together with cell proliferation and differentiation, the phenomenon known as "apoptosis". This physiological process of the eukaryotic cells death is used by many parasites in parasite--host relationships in different epitopes.

[Cosmetic results of posttraumatic eyeball subatrophy surgical treatment using "alloplant" biomaterials with subsequent use of prostheses].

A complex of surgical operations making use of Alloplant biomaterials, performed in 47 patients with initial posttraumatic subatrophy and 79 patients with well-developed and far advanced stages of this condition, helped preserve the eye as anatomical organ in 97.5% patients, with enlargement of the eyeball in two-thirds of patients and stabilization in one-third. Optic reconstructive operations were later performed and visual acuity improved in patients with the initial stage of subatrophy.

[The effect of aqueous extracts of hepatotropic medicinal plants on free-radical oxidation processes].

The authors studied the effect of decoctions and infusions of medicinal plants (common barberry, sandy immortelle, common maize, spotted milk thistle) on free-radical oxidation (FRO) in model systems in vitro and in experiments in vivo on nonbred albino mice. In various model systems (in which active forms of oxygen are generated and lipid peroxidation takes place) the plants under study suppressed as well as intensified the processes of lipid peroxidation, depending on the concentration of the phytopreparation and the type of the model systems. In in vivo experiments the drugs of plant origin suppressed lipid peroxidation, reducing the parameters induced by iron and chemoluminescence and the malonic dialdehyde level in the liver.

[Effect of rifampicin, endotoxin, and their combination on the phagocyte activity, microsomal oxidation, and free radical processes in the liver].

Experiments were conducted on mices to study the effect of strain MRe-600 Escherichia coli endotoxin, rifampicin, and their combination at the level of cytochrome p-450, b5, aminopyrine N-demethylase and aniline-r-hydroxylase activity in the liver, absorptive activity and oxygen dependent metabolism of macrophages, and free-radical processes in the liver. It was found that rifampicin removes the endotoxin-induced depression of microsomal oxidation in the liver, but potentiates the stimulating effect of the endotoxin on macrophageal absorptive activity and the "respiratory outburst" in these cells. The oxidative equilibrium in the liver in this case does not change.

[The immunotropic properties of biologically active products obtained from Klamath weed (Hypericum perforatum L.)].

We carried out a systematic study of immunotropic activity of John's wort on the level of integrated fractions including all basic active substances of this plant. Both types of substances capable of increasing and suppressing the immunity were found in John's wort. Polyphenol fraction exhibits the immunostimulating activity with respect to the system of mononuclear phagocyte system, cellular and humoral immunity, and is capable of recovering the immune response in conditions of high-zone tolerance.

[Prodigiozan modulation of the specific activity of antidepressants].

The experiments carried out on mongrel male mice showed that bacterial lipopolysaccharide Prodigiozan inhibit the activity of P-450-dependent monooxygenases of the liver, thus changing the activity of antidepressants--amitriptyline and imipraminum. The data on biological activity were tested in "tail suspension" test. Prodigiozan exhibited no central effect.

[The interaction of the immune system and the liver mono-oxygenase system].

The effect of different immunostimulants (prodigiosan, levamisole, T-activin, sodium diethyl dithiocarbamate, sodium nucleinate, lithium chloride, muramil dipeptide, B-activin) and mixed hepatic function oxidase inhibitors (cimetidine, chloramphenicol) or inducers (phenobarbital, flumecinol, rifampicin) on immune reactivity (macrophage function, humoral and cellular responses) and hepatic microsomal function (hexobarbital sleeping-time) was studied in non-inbred and BALB/c male mice. There was a high correlation between the ability of immunostimulants to depress hexobarbital metabolism and their ability to enhance macrophage activity (carbon clearance test), but not humoral and cellular immunity. No reciprocal changes occurred in immune reactivity after positive or negative pharmacological modulation of hepatic drug metabolizing enzyme activity.

[The pharmacokinetic and immunopharmacological aspects of prodigiozan interaction with psychotropic agents].

In experiments on white male mice it was found that an immunostimulant prodigiozan suppresses the activity of cytochrome P-450-dependent liver monohygenases that results in modulation of the activity of neuroleptics (aminazine and haloperidol) administered against its background. Their activity is assessed by the "open field "test" and the "tail suspension test". One could observe a delay of the occurrence of the neuroleptics' effect and prolongation of the effect.

[Immunostimulants and autoimmunity].

The review presents the recent data on the use of immunity stimulants (thymus peptides, synthetic immunomodulators, immunostimulants of bacterial origin) under conditions of experimental autoimmunity and in clinic. A brief characteristic of the immunotropic activity of the drugs is given, the mechanisms of their action on the formation of the autoimmune response and clinical effectiveness are analyzed.

[The effect of stimulants of immunity on anti-infective resistance and on the activity of the liver monooxygenase system].

The effect of some immunostimulants (bacterial lipopolysaccharide prodigiosan, active thymic peptide T-activin, synthetic compound levamisole) on the anti-infection resistance and metabolic function of the liver (hexobarbital sleeping-time) was studied on noninbred male mice. It was found that when administered in doses and under schedules that protected mice against lethal infection (Pseudomonas pyocyanea, i.p.

[Immunomodulating therapy of adjuvant disease in rats using cyclophosphamide in combination with prodigiozan--its effect on anti-infectious resistance].

The effect of immunomodulating therapy of adjuvant disease in rats with cyclophosphamide, prodigiozan and their combinations on infection resistance, weight of the lymphoid organs and leukocyte counts in peripheral blood, as well as the effect of prodigiozan on acute toxicity of cyclophosphamide in intact mice and mice exposed to the Freund's complete adjuvant (FCA) was studied. Prodigiozan did not increase acute toxicity of cyclophosphamide in the intact mice. It lowered the cyclophosphamide toxicity at the background of the FCA and decreased the levels of leukopenia induced by the immunosuppressor in the rats with adjuvant arthritis.

[Immunomodulating therapy of adjuvant disease in rats].

During a comparative analysis of efficacy of prodigiosan and its combinations with cyclophosphamide (5 mg/kg), asathioprine (4 and 20 mg/kg) and delagil (25 mg/kg) it was shown that the most pronounced suppression of the adjuvant disease was observed in the group of animals given cyclophosphamide with prodigiosan. The suppression of arthritis with cyclophosphamide, prodigiosan and their combination was followed by a decrease of autosensibility parameters--hypersensitivity to collagen and the amount of immune rosette-forming cells in the regional lymph nodes.