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Experiments on random-bred albino mice showed that of β2-adrenoreceptor agonist hexaprenaline sulfate significantly reduced mortality of mice from experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h after modeling by reducing blood levels of proinflammatory cytokines TNFα, IL-1β, and IL-6. The antagonist of β2AR ICI-118,551 eliminated this effect.

Experiments on random-bred albino mice showed that NF-κB inhibitor (BAY 11-7082) and β2-adrenoreceptor agonist (dexmedetomidine hydrochloride) significantly reduced mouse mortality in 4 and 24 h after sepsis modeling (intraperitoneal administration of E. coli) by reducing blood levels of proinflammatory cytokines TNFα, IL-1β, and IL-6. The combined administration of NF-κB inhibitor and β2-adrenoreceptors agonist have an additive effect.

Experiments on outbred albino rats showed that chronic nitrile acrylate intoxication (60 days, 0.05 LD50 per day subcutaneously) led to reduction of T-dependent humoral immune response (T-independent humoral immune response was less affected); parameters cell immunity were suppressed to a greater extent than parameters of humoral immune reactions. Equal attenuation of the functions of Th1 and Th2 lymphocytes, decrease of the blood levels of immunoregulatory, pro- and anti-inflammatory cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-13), and decrease of acetyl cholinesterase activity in thymic and splenic T lymphocytes were observed.

Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine receptor agonist (TBPB) and α7n-acetylcholine receptor agonist (GTS-21) significantly reduced mortality of mice with experimental sepsis (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by reducing blood concentration of proinflammatory cytokines TNF-α, IL-1β, and IL-6. Combined treatment with TBPB and GTS-21 determined their additive effect.

Experiments on albino outbred rats showed that chronic poisoning with organophosphorus compounds (Russian VX, and sarin) for 30 days in a total dose of 0.3 DL50 (0.01 DL50 daily) is followed by a decrease in phagocytic and metabolic activity of neutrophils. The reduction of functional activity of monocyte phagocytic system was stipulated by the stimulation of N-cholinergic receptors of these cells. These changes were accompanied by a decrease in blood concentration of proinflammatory cytokines (TNF-α, IL-1β, and IL-6).

Experiments on outbred albino mice have shown that proserine (reversible cholinesterase inhibitor) and nicotine (nicotinic receptor agonist) in a equivalent dose of 0.2 DL(50)injected 2 h before sepsis induction significantly reduced animal mortality from experimental infection due to reduction of blood concentrations of proinflammatory cytokines TNF-α, IL-1β, and IL-6.

Experiments on outbred mice showed that acetylcholine chloride in a dose of 20 mg/kg 6 h after subcutaneous injection significantly reduces mortality of mice from sepsis induced by intraperitoneal injection of 2×10(9) E. coli bacterial bodies and the blood levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6.

Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1β, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.

Experiments on Wistar rats showed that subacute poisoning with anticholinesterase toxicants zarin and agent VX (daily subcutaneous injections in 1/7 LD50 for 6 days) led to suppression of cellular and humoral immune reactions and to a decrease in blood concentrations of cytokines (IL-2, IL-4, IFN-gamma) with a reduction of the IFN-gamma/IL-4 and IL-2/IL-4 ratios, which attests to more pronounced decrease in Th1 lymphocyte function in comparison with Th2 cells.

Experiments on outbred albino rats showed that single intraperitoneal injection of cytochrome P-450 inhibitor 2-diethylaminoethyl-2,2-diphenylpropylacetate (SKF-525A) in a dose of 50 mg/kg before acute poisoning with 1,2-dichloroethane and trichloroethane in a dose of 1.0 LD(50), metabolized in the body to compounds with higher toxicity (the phenomenon of "lethal synthesis") reduced their immunotoxicity by decreasing the formation of their biotransformation products.

Acute poisoning with tetrachloromethane in a dose of 0.75 LD(50) suppressed humoral and cell immune reactions in Wistar rats. Immunotoxicity of tetrachloromethane is realized via initiation of lipid peroxidation and inhibition of acetylcholine esterase in T lymphocytes and alpha-naphthyl AS-acetate esterase and alpha-naphthyl butyrate esterase in splenocytes.

Acute poisoning with alcohols and cholinotropic preparations carboxyphosphamide and atropine (0.8 LD(50)) was modeled on male outbred mice weighing 18-24 g. The decrease in activity of natural killer cells was most pronounced after injection of atropine, but insignificant after treatment with ethanol. The inhibitory effect of ethylene glycol, methanol, and methanol on functional activity of natural killer cells in vitro directly depended on their concentration. The effects of alcohols in equimolar concentrations of 10, 100, and 500 mM were similar. Therefore, immunotoxicity of alcohols was associated with the action of their metabolites. The ability of products formed after biotransformation of ethylene glycol, methanol, and ethanol in equimolar concentrations to cause damage to natural killer cells decreased in the following order: glyoxylic acid>formic acid>acetaldehyde>glycolaldehyde>glycolic acid. T-Activin injected subcutaneously in doses of 2.5 and 5.0 microg/kg for 3 days normalized activity of natural killer cells suppressed after acute poisoning with alcohols and cholinotropic preparations.

Experiments on Wistar rats showed that acute poisoning with chemicals in a dose of 0.75 LD(50) (dimethyl dichlorovinyl phosphate, sarin, VX substance, sulfur yperite, lewisite, tetraethyl lead, dichloroethane) inhibiting platelet acetylcholine esterase, alpha-naphthyl-AS-acetate esterase, and alpha-naphthyl-butyrate esterase suppressed T cell-mediated immune reactions.

Experiments on noninbred albino rats showed that a chronic exposure to organophosphorus compounds (carbophos and metaphos, 30 days, total dose 0.3 LD50) is primarily followed by a decrease in the immune reactions and IFN-γ associated with Th1 lymphocyte function (in comparison with the immune response due to activation of Th2 cells by IL-4). The concentrations of IL-2, IL-6, and IL-10 in the blood decreased after 30-day intoxication. The immune reactions associated with functional activity of Th1 and Th2 lymphocytes were shown to decrease similarly after chronic treatment with organophosphorus compounds for 60 days (total dose 0.6 LD50). This exposure was accompanied by a decrease in the concentrations of IFN-γ, IL-4, IL-2, and IL-6, but had no effect on the level of IL-10 in the blood.

Stimulation of nicotinic and muscarinic cholinoreceptors (nAChR, mAChR) in outbred albino mice with nicotine and aceclidine, respectively, in single equilethal doses 0.5 DL50 6 h before sepsis induction signifi cantly reduced animal mortality due to a decrease in blood concentrations of proinfl ammatory cytokines IL-1β, IL-6, and MIP-2. Stimulation of mAChR (injection of aceclidine) stimulated the neutrophilic phagocytic and metabolic activity. Realization of the cholinergic anti-infl ammatory pathway (stimulation of the peripheral nicotinic cholinoreceptors (α7nAChR) and central muscarinic cholinoreceptors (mAChR) was modulated by stimulation of the muscarinic cholinoreceptors of the phagocytic monocytic system cells.

Experiments of outbred albino rats showed that chronic ethanol intoxication (20 days, summary dose 5 LD(50)) inhibited immune reactions mainly mediated by Th1-cells, increased blood corticosterone concentration, reduced T-lymphocyte acetylcholinesterase activity, blood concentrations of IFN-γ, IL-2, IL-4, IL-10, and increased IL-6 level.

Experiments on Wistar rats showed that the combined action of mechanical trauma and organophosphorus compound dimethyl dichlorovinyl phosphate a dose of 0.8 LD50 was accompanied by summation of their immunosuppressive effects. We observed an additive effect in relation to stimulation of the adrenal cortex. Treatment with general chemical toxicants (acrylic acid nitrile and acetonitrile, 0.8 LD50) alone or in combination with mechanical trauma produced similar increase in plasma corticosterone concentration. This effect was short-lasting and less pronounced compared to the influence of dimethyl dichlorovinyl phosphate. The immunosuppressive effect of trauma and nitriles is primarily related to the influence of poisons.

In vitro experiments on splenocytes from noninbred mice showed that ethylene glycol, methanol, and ethanol dose-dependently suppressed functional activity of T and B cells. These compounds in equimolar concentrations (10, 100, and 500 mM) produced similar effects, hence their immunotoxicity is determined by their metabolites. The suppressive effects of alcohol biotransformation products to antibody-forming activity of T and B cells decreased in the following order: glyoxylic acid - formic acid - glycolaldehyde - glycolic acid - acetaldehyde. The effects of these substances were dose-dependent. Suppression of T cells was more pronounced.

Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyl dichlorovinyl phosphate (0.5 LD50) was accompanied by two opposite effects: inhibition of acetylcholinesterase in T lymphocytes leading to suppression of thymus-dependent antibody formation (predominant effect) and acetylcholine-induced stimulation of antibody production. Acetylcholine activated acetylcholinesterase in intact T cells.

Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyldichlorovinylphosphate (0.2 and 0.8 LD50) was accompanied by suppression of the major immune reactions. Increasing the concentration of epinephrine and norepinephrine in the plasma produced less pronounced opposite effects, except for the influence on natural killer activity.

Experiments on outbred albino rats showed that administration of acetylcholine and aceclidine in a dose of 0.1 LD50 for 3 days and of dimethyl dichlorovinyl phosphate (organophosphorus compound) in a single dose of 0.05 LD50 stimulated the function of Th1 and Th2 lymphocytes and cytokine production by these cells. Dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 produced an opposite effect. Acetylcholine and aceclidine stimulated activity of acetylcholinesterase in T cells, while dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 inhibited it. During acute intoxication, the organophosphorus compound, depending on the dose, can stimulate (acetylcholine effect) and inhibit the immune reactions (acetylcholinesterase inhibition of T cells).

Experiments on random-bred male rats shows that acute poisoning with metaphos and acrylonitrile inhibites mainly the thymus-dependent humoral immune response, delayed type hypersensitivity reaction, and activities of natural killers and K cells. The increase in plasma corticosterone under the effect of metaphos ensures the participation of this hormone in the realization of suppression of natural killers and thymus-dependent humoral immune response (production of IgG), the contribution of the hormone to this suppression being 35.6 and 35.1%, respectively. Suppression of immune reactions by acrylonitrile is not associated with corticosterone effect.

Acute poisoning of rats with acetonitryl (0.3 and 0.8 LD50) decreased the bactericidal activity of the blood serum, serum activities of lysozyme and β-lysines, functional activity of neutrophils, counts of splenocytes producing antibodies to T-dependent and thymus-independent antigens, natural and antibody-dependent cytotoxicities, antigen-presenting function of macrophages, and delayed type hypersensitivity. The content of corticosterone in the plasma decreased under the effect of acetonitryl after 2 days. The effects of acetonitryl are dose-dependent.

Subjects with various types of personality accentuation are characterized by specific features of immunity. This proves a relationship between the function of the central nervous and immune systems. The detected features of immune response in subjects with various types of personality accentuation can be important for the formation of immunosuppression or hypersensitivity in various diseases.

Experimental acute dichloroethane intoxication (0.75 LD50) weakens the anti-infection resistance, suppresses antibody-dependent cell-mediated cytotoxicity, delayed-type hypersensitivity, and T-dependent humoral immune response and reduces the number of colony-forming units in the spleen. This suppression is probably associated with inhibition of α-naphthyl-AS-acetate esterase in immunocytes.

Oral treatment of experimental random-bred albino rats with inductors of the monooxygenase system phenobarbital (50 mg/kg) and benzenal (70 mg/kg) for 3 days until acute poisoning with toxins (methanol, ethylene glycol, and dichloroethane in doses of 1.0 LD50) metabolizing in the body to compounds with higher toxicity (phenomenon of lethal synthesis) increased immunotoxicity of these inductors.

Acetylcholine and aceclidine reduce the mortality of mice after irradiation. This effect is evidently due to activation of M-cholinoreactive structures leading to an increase of the number of colony-forming units in the spleen, migration of T and B lymphocytes from lymphoid organs, and boosting of antibody production and of antibody-dependent cell cytotoxicity.

Experiments on mice revealed that the cholinesterase reactivator dipiroxime in a single dose of 15 mg/kg and retinol acetate in a dose stimulating thymus-dependent antibody production (3000 U per os daily for 3 days after poisoning) reverse the suppression of the main immune reactions caused by dimethyl dichlorovinylphosphate.

Cholinergic stimulation (acetylcholine, aceclidine, armin) is found to improve antiinfectious nonspecific resistance in mice. The effect depends on the dose of cholinomimetic (armin), is maximal during the first 18 hours of the infectious process, and is determined by serum antibacterial activity, lysozyme activity, and the function of neutrophils and natural killers.

Experiments on Wistar rats showed that acute poisoning with chemicals in a dose of 0.75 LD(50) (dimethyl dichlorovinyl phosphate, sarin, VX substance, sulfur yperite, lewisite, tetraethyl lead, dichloroethane) inhibiting platelet acetylcholine esterase, alpha-naphthyl-AS-acetate esterase, and alpha-naphthyl-butyrate esterase suppressed T cell-mediated immune reactions.

Acute poisoning with alcohols and cholinotropic preparations carboxyphosphamide and atropine (0.8 LD(50)) was modeled on male outbred mice weighing 18-24 g. The decrease in activity of natural killer cells was most pronounced after injection of atropine, but insignificant after treatment with ethanol. The inhibitory effect of ethylene glycol, methanol, and methanol on functional activity of natural killer cells in vitro directly depended on their concentration. The effects of alcohols in equimolar concentrations of 10, 100, and 500 mM were similar. Therefore, immunotoxicity of alcohols was associated with the action of their metabolites. The ability of products formed after biotransformation of ethylene glycol, methanol, and ethanol in equimolar concentrations to cause damage to natural killer cells decreased in the following order: glyoxylic acidformic acidacetaldehydeglycolaldehydeglycolic acid. T-Activin injected subcutaneously in doses of 2.5 and 5.0 microg/kg for 3 days normalized activity of natural killer cells suppressed after acute poisoning with alcohols and cholinotropic preparations.

Experiments on Wistar rats showed that the combined action of mechanical trauma and organophosphorus compound dimethyl dichlorovinyl phosphate a dose of 0.8 LD50 was accompanied by summation of their immunosuppressive effects. We observed an additive effect in relation to stimulation of the adrenal cortex. Treatment with general chemical toxicants (acrylic acid nitrile and acetonitrile, 0.8 LD50) alone or in combination with mechanical trauma produced similar increase in plasma corticosterone concentration. This effect was short-lasting and less pronounced compared to the influence of dimethyl dichlorovinyl phosphate. The immunosuppressive effect of trauma and nitriles is primarily related to the influence of poisons.

In vitro experiments on splenocytes from noninbred mice showed that ethylene glycol, methanol, and ethanol dose-dependently suppressed functional activity of T and B cells. These compounds in equimolar concentrations (10, 100, and 500 mM) produced similar effects, hence their immunotoxicity is determined by their metabolites. The suppressive effects of alcohol biotransformation products to antibody-forming activity of T and B cells decreased in the following order: glyoxylic acid - formic acid - glycolaldehyde - glycolic acid - acetaldehyde. The effects of these substances were dose-dependent. Suppression of T cells was more pronounced.

Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyldichlorovinylphosphate (0.2 and 0.8 LD50) was accompanied by suppression of the major immune reactions. Increasing the concentration of epinephrine and norepinephrine in the plasma produced less pronounced opposite effects, except for the influence on natural killer activity.

Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyl dichlorovinyl phosphate (0.5 LD(50)) was accompanied by two opposite effects: inhibition of acetylcholinesterase in T lymphocytes leading to suppression of thymus-dependent antibody formation (predominant effect) and acetylcholine-induced stimulation of antibody production. Acetylcholine activated acetylcholinesterase in intact T cells.

Experiments on outbred and inbred male CBA mice showed that acute poisoning with ethylene glycol (0.8 LD50) increased mortality from infections, decreased the number of spleen colony-forming units, inhibited antibody formation (mainly to thymus-dependent antigens, and suppressed natural and antibody-dependent cytotoxicity and delayed-type hypersensitivity. Ethylene glycol in concentrations of 10 and 100 mM in vitro inhibited the formation of antibody-producing cells by acting on T and B lymphocytes.

Cholinesterase reactivator dipyroxime and hydrogen cyanide antidote anticyan partially restore cell and humoral immune response in mice after acute acrylonitrile poisoning (0.5 LD(50)). When used in combination these drugs virtually completely prevented the suppression of immune reactions. The main mechanism of immunotoxic effect of acrylonitrile is mediated through inhibition of T lymphocyte esterases and a(3) component of cytochrome c oxidase of immunocyte mitochondrial respiration enzymes, which is important for prevention and treatment of immune disturbances caused by this toxin.

Experiments on outbred and inbred male CBA mice showed that acute poisoning with ethylene glycol (0.8 LD50) increased mortality from infections, decreased the number of spleen colony-forming units, inhibited antibody formation (mainly to thymus-dependent antigens, and suppressed natural and antibody-dependent cytotoxicity and delayed-type hypersensitivity. Ethylene glycol in concentrations of 10 and 100 mM in vitro inhibited the formation of antibody-producing cells by acting on T and B lymphocytes.