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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.

It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

It was established in experiments on noninbred albino rats that acute intoxication with malathion (0.75 LD50) reduced the function of Th1 cells more significantly than the function of Th2 lymphocyte, decreases the activity of B cells and NK cells, blood levels of TNFa, IL-1b and IL-6, IFN-g, IL-2, and IL-4, while not significantly affecting the concentration of IL-10 and IL-13. Atropine (10 mg/kg) under conditions of acute malathion intoxication improved the function of T cells and B lymphocytes, NK cells, as well as the synthesis of immunoregulatory cytokines IFN-g, IL-2, and IL-4. At the same time, atropine in malathion intoxicated rats had no effect on suppression of the synthesis of proinflammatory cytokines TNF, IL-1g and IL-6 as well as the content of anti-inflammatory cytokines IL-10 and IL-13.

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 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.

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.

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 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.

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.

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 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.

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.