• Environmental Analysis Health and Toxicology
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• 제19권4호
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• pp.367-373
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• 2004

Mancozeb, a polymeric complex of zinc and manganese salts of ethylene bisthiocarbamate (EBDC), is used widely in agriculture as fungicides, insecticides, and herbicides. Mancozeb can be occupationally and environmentally exposed to human and has been reported to induce estrogenic activity, therein it is considered as an endocrine disrupter. After female ICR mice were treated Mancozeb orally at the doses of 250, 1,000 and 1,500 mg/kg/day for consecutive 30 day, we investigated the effects of Mancozeb on the immunopathological parameters (body-, thymus-, spleen-, liver- and kidny-weight, splenic cellularity, hematological parameters) and mitogen (Con A, LPS)-induced splenocyte proliferation (SP). Liver- and kidney- weight were increased, but body- and thymus-weight, number of splenocytes and WBC were decreased, when compared with control group. When splenocytes isolated from the mice exposed to Mancozeb for 30 days were cultured in presence of mitogens, the SP against Con A was significantly and dose-dependently decreased and the SP against LPS was also slightly decreased. Our present results indicate that subacute exposure of Mancozeb to mice might show immunotoxic effect.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.207-215
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• 2009

Despite wide therapeutic use of CpG ODN against infection, allergy and cancer, the safety and toxicity of CpG ODNs were poorly delineated. Thus, we investigated whether optimal dosing of CpG ODN would affect immunotoxicological parameters in NZB/NZW F1 mice. Comparisons were made among control, non-CpG ODN and mouse CpG ODN ($10{\mu}g$)-treated groups for 4 weeks. To gauge the immunotoxicity of CpG ODNs, we measured nonspecific parameters, degree of lupus nephritis, proteinuria, or autoantibody, and cytokine expression in mRNA level of lymphocytes. We found that there were no significant differences among groups in nonspecific immunotoxicological profiles and in evaluation profiles of glomerulonephritis. However, titer of anti-dsDNA and anti-cardiolipin antibodies in mouse CpG ODN group rose three or eight-fold higher than in control group. Collectively, CpG ODN might be clinically less immunotoxic in terms of clinical profiles in lupus-prone NZB/NZW F1 mice, in spite of high autoantibody titer in CpG ODN treated groups.

• Journal of Microbiology and Biotechnology
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• 제7권1호
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• pp.56-61
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• 1997

A strain producing immunosuppressive substances was isolated from a soil in Cheju island. By morphological, cultural, and physiological studies, the strain was identified as Streptomyces lydicus MCY-524. Cultured broth was purified by silica gel, sephadex LH-20 and preparative HPLC and gave two immunosuppressive compounds, MCH-22 and MCH-32. They dramatically suppressed the B cell activation with lipopolysaccharide, T cell activation by mixed lymphocyte response, and primary T-dependent antibody response at a final concentration of 1 ${\mu}g$/ml. They also markedly suppressed the proliferation of lymphocytes induced by lipopolysaccharide, pokeweed mitogen, and concanavaline A at the same concentration. Their suppressive activities, which were comparable to those of cyclosporin A, suggested that they were potent and broad immunotoxic agents on the immune functions of murine lymphocytes.

• Environmental Analysis Health and Toxicology
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• 제13권1_2호
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• pp.33-41
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• 1998

Chlorpyrifos, o,o diethyl-o-(3,5,6-trichloro-2-pyridyl) phosphorothioate, is a broad spectrum organophosphate insecticide. The use of chlorpyrifos has been increased more and more as pesticide. But the effects of chlorpyrifos on the immune alterations has not been yet observed. Therefore, we investigated the effects of chlorpyrifos on the immune alterations in CICA male mice. Chlorpyrifos was administered to mice by a single intraperitoneal injection for the purpose of observing acute effects. On the one hand to get the information on immunopathologic alterations we observed hematological values, counted total circulating leukocytes and assessed the ratio of lymphocytes and neutrophils from the peripheral blood, measured the ratio of organ/body weight and counted splenic cellularity in CBA male mice which treated chlorpyrifos intraperitoneally. But we could not find any significant immunopathologic alterations statistically by a single intraperitoneal injection. Also, the exposure of chlorpyrifos caused no significant change in the number of PFC/10$^6$ spleen cells at any three given doses. On the other hand a singte intraperitoneal injection of chlorpyrifos decreased the lymphocyte proliferation response slightly to ConA or LPS stimulation at a dose of 6 mg/kg b.w. Administrations of chlorpyrifos reduced mixed leukocyte response(MLR). MLR was decreased moderately at doses of 3mg/kg b.w. and 6mg/kg b.w. Therefore, all these findings suggest that chlorpyrifos may alter the immune functions acutely. especially by the changes of T lymphocyte activity.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.446-454
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• 2009

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-$\alpha$. In the present study, adverse effects of FPP-3 on immune functions were determined in female BALB/c mice. When mice were administered orally with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days, FPP-3 suppressed the number of antibody-forming cells and reduced thymus weight at 500 mg/kg. In addition, FPP-3 administered mice exhibited reduced splenic cellularity and numbers of splenocyte subsets, such as $CD3^+$ cells, $CD3^+CD4^+$ cells, $CD3^+CD8^+$ cells and macrophages. IL-4 mRNA expression was significantly suppressed by FPP-3 treatment. Moreover, the number of $CD4^+IL-4^+$ cells was reduced following the treatment of mice with 500 mg/kg of FPP-3. These results suggested that FPP-3 at 500 mg/kg might be immunotoxic, and that FPP-3-induced immunotoxicity might be mediated, at least in part, through the inhibition of cytokine production, such as IL-4.

• 약학회지
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• 제44권1호
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• pp.1-8
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• 2000

Effects of Astragali radix extract (AG) on the humoral immunotoxic responses of zinc chloride (Zn) were studied in ICR mice. Mice were divided into 4 groups (10 mice/group), and Zn was given to the mice, 1 hr after i.p. injection with 0.5 g/kg of AG, by i.p. injection daily for 10 days at a dose of 25 mg/kg. Mice were immunized and challenged with sheep red blood cells (SRBC). Zn treatment increased the relative weight of spleen compared with those in controls, but decreased the hemagglutination (HA) titer 2-mercaptoethanol-resistant HA (MER-HA) titer and splenic plaque forming cells (PFC). AG treatment significantly increased the relative weight of spleen, HA titer and PFC compared with those in controls. Combination of Zn and AG significantly increased the relative weight of spleen compared with those in controls, but decreased the HA titer, MER-HA titer and PFC. The relative weight of spleen was significantly increased in the Zn and AG combination group than those in Zn alone treatment group. But the HA titer, MER-HA titer and PFC were slightly increased in the group of combination. These results suggest that AG might slightly restore humoral immune responses lowered by an excess of zinc.

• Journal of Preventive Medicine and Public Health
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• 제32권3호
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• pp.347-354
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• 1999

Objective: This paper examines the possible toxicity to immune system in farmers chronically exposed to pesticides. Methods : We compared 43 male farmers exposed to pesticides with 29 male residents who had neither past nor current pesticides exposure. The selected variables for studying immunotoxicity were WBC, CD3, CD4, CD8, CD19, CD56, IgG, IgA, IgM, and IL-2. As part of the baseline questionnaires for the immunotoxicity, subjects were asked about kinds of farming, posticides exposure and medical history. Results : None of the variables for studying immunotoxicity showed statistically significant difference between the two groups. Although the results were not statistically significant, CD4 and the CD4/CD8 ratio decreased and CD8 increased. These effects showed a dose response change with exposure level. In the exposed group, the values of CD3, CD4, CD4/CD8 and CD19 decreased and those of the CD8 and CD56 increased compared to the non-exposed group. Also there was higher prevalence of self-reported disease in the exposed group compared to the non-exposed group. Conclusions: Although statistically significant differences in indices of immunotoxicity in farmers exposed to pesticides were not shown, the results suggest that pesticides may decrease immune function. More advanced test methods for immunotoxicity need to be developed and tested in larger population to detect immunotoxic effects of pesticides.

• Toxicological Research
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• 제11권1호
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• pp.15-21
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• 1995

Several populations of lymphocytes possess receptors for autonomic neurotransmitter, which make lymphocytes susceptible to autonomic stimulation. This study was to evaluate the functional alternation of effector cells of the immune system. Female Balb/C mice, 15-20 g, were injected with MA subcutaneously under various conditions. Mixed lymphocyte reaction (MLR) showed certain T cell subsets were affected by MA. The level of interleukin-2 (IL-2) production was inhibited due to a defect in expression of the IL-2 receptor. In mice injected with 20 mg MA/kg, 1 day before assay, phagocytosis of peritoneal macrophages showed $14.07\pm3%$, which was similar degree to 5 mg MA/kg treatment for 4 consecutive days. Phagocytosis was almost recovered to that of control after 4 day in 20 mg/kg injected mice. Maximum inhibition of plaque forming cell (PFC) occurred when MA was given early, indicating the inductive time point of antibody production was affected. The cortisol level increased in the MA treated group (0.05, 0.20, and $0.08{\mu}g$/dl for control, low, and high dose-MA treated mice, respectively). Based on these results, MA has general suppression effects on the immune systems by functional alteration of effector cells. Considering the increment of serum cortisol levels, MA partially impacts the neuroendocrine system to lead to failure of immune response.

• Toxicological Research
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• 제17권2호
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• pp.115-121
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• 2001

Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg$\cdot$ body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg$\cdot$b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg$\cdot$b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3$^{+}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) and CD3$^{-}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.

• Toxicological Research
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• 제15권1호
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• pp.39-45
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• 1999

To investigate the preventive effects of melatonin (MLT) on the immunotoxicity of cadmium acetate[Cd(AC)2] in ICR mice, Mlt(10,50mg/kg as cadmium) were orally administered to mice once a day (5:00, PM) for 28 consecutive days. Cadmium(Cd) test solution was also administered at 25mg/kg of cadmium through the same route 2hr after administration of MLT daily, Mice were immunized and challenged with sheep red blood cells (SRBC). Immune functions evaluated were delayed type hypersensitivity (DTH) response, mitogenic response, and flow cytometry analysis. The results of these studies were summarized as follows ; DTH response was abnormally increased in mice treated with Cd alone. DTH response was normally depressed in mice treated with Cd plus MLT along with the increase of MLT doses. The mitogenic response of splenic T cell to Con A and that of B cells to LPS was remarkably increased by MLT treatment as compared with treatment of Cd alone In case of CD 8+ cells, the slight increase was observed in MLT treatment. Splenic T cells and B cells were significantly increased by MLT treatment as compared with treatment with Cd alone. These results suggest that MLT has significant preventive effects on the immunotoxic status induced by Cd exposure.