Immunotoxic effects

The immune system is a highly integrated and regulated network of cell types that requires continual renewal to achieve balance and immunocom-petence. The delicacy of this balance makes the immune system a natural target for cytotoxic drugs or their metabolites. Since renewal is dependent on the ability of cells to proliferate and differentiate, exposure to agents that arrest cell division can subsequently lead to reduced immune function or immunosuppression. This concept has been exploited in the development of therapeutic drugs intended to treat leukemias, autoimmune 

cells T], cells that are specifically sensitized to antigens on target cells interact directly with target cells to lyse them. 

Td Cells involved in delayed hypersensitivity that act indirectly to kill target cells T cells react with antigen and release cytokines that can kill target cells. 

NK cells Nonspecific T cells that react directly with target cells (tumor cells) without prior sensitization. 

Null cells Antibody-dependent cell-mediated cytotoxicity (ADCC) involving non-T/non-B cells (null cells) with F, receptors specific for antibody-coated target cells. 

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The database for the health effects of methyl parathion after ingestion in experimental animals is substantial. However, as can be seen in Figure 3-5, only limited information is available on the effects of inhalation and dermal exposure to methyl parathion in animals. Furthermore, the health effects such as death and neurotoxicity resulting from acute exposure in animals are more fully studied than systemic and immunotoxic effects associated with acute exposure. 

Immunotoxicity. Only a single case report of skin allergy to methyl parathion has been reported in humans (Lisi et al. 1987). No studies are available in humans exposed to methyl parathion via the inhalation or oral route. Based on limited animal studies, immunotoxicity may be a sensitive end point of methyl parathion-induced toxicity (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). Thus, humans may be at risk for adverse immunological effects following exposure to methyl parathion. The limited information available on the effects of combined exposure to methyl parathion suggest the its toxicity is not route-dependent. Therefore, there is no reason to suspect that the immunotoxic effects observed following oral exposure of animals are route-specific. 

Institoris L, Siroki O, Toth S, et al. 1992. Immunotoxic effects of MPT-IP containing 60% methyl parathion. Hum Exp Toxicol 11 11-16. 

Rodgers KE, Leung N, Imamura T, et al. 1986. Rapid in vitro screening assay for immunotoxic effects of organophosphorus and carbamate insecticides on the generation of cytotoxic T lymphocyte responses. Pestic Biochem Physiol 26 292-301. 

Khurana SK, Chauhan RS, Mahipal SK. 1998. Immunotoxic effects of cypermethrin and endosulfan on macrophage functions of broiler chicks. Indian Journal of Animal Sciences 68(2) 105-106. 

Holladay, S.D., S.A. Smith, R.M. Gogal, E.G. Besteman, T. Hrubec, A.S.M.I. Deyab, and S.A. Ahmed. 1996. Morphologic lesions and acute immunotoxic effects in tilapia (Oreochromis niloticus) exposed to benzo[a]pyrene. IAAAM Proc. 27 59. 

Savabieasfahani, M., R.L. Lochmiller, D.P. Rafferty, and J.A. Sinclair. 1998. Sensitivity of wild cotton rats (Sigmodon hispidus) to the immunotoxic effects of low-level arsenic exposure. Arch. Environ. Contam. Toxicol. 34 289-296. 

Immunotoxicology studies the effects of xenobiotics on the immune system an immunotoxic compound is defined as a compound that can alter one or more immune functions, resulting in an adverse effect for the host. In particular, two main immunotoxic effects can be identified ... 

In general, compounds that are capable of damaging or destroying the bone marrow will often have a profoundly immunotoxic effect, since the marrow is the source of im-... 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

Consumption of fish oil in excess can generate immunotoxic effects in laboratory animals. Rats fed a 17% fish oil diet had reduced wound-healing responses when compared to com oil [59], In a mouse model of bacterial resistance to S. typhimurium, lower survival rates were reported for those animals that ingested a 20% fish oil diet over 15 days [59], Similar fish oil-induced effects in guinea pigs were noted in a study of experimental tuberculosis leading the authors to conclude that this treatment resulted in decreased resistance to infectious disease. The consumption of fish oil has also been reported to result in alterations of hemostatic parameters such as platelet production and function. However, there is no indication that at doses normally consumed by humans, immunotoxicity will occur. 

Kim, D. and Lawrence, D.A., Immunotoxic effects of inorganic lead on host resistance of mice with different circling behavior preferences, Brain Behav. Immun. 14, 305, 2000. 

The vast majority of information regarding the immunotoxic effects of different chemicals has been derived from laboratory studies of vertebrate responses in which the mechanism of action is evaluated and the subsequent effects on different immune parameters and susceptibility to infection is determined. It is much harder to extrapolate... 

Filipov, N. M. et al.,. Immunotoxic effects of short-term atrazine exposure in young male C57BL/6 mice, Toxicol. Sci., 86, 324, 2005. 

Immunotoxic Effects of Environmental Chemicals on Adult Amphibians.. 388... 

Hart, L.J. et al., Subacute immunotoxic effects of the polycyclic aromatic hydrocarbon 7,12-dimethylbenzanthracene (DMBA) on spleen and pronephros leukocytic cell counts and phagocytic cell activity in tilapia, Oreochromis niloticus, Aquat. Toxicol., 41, 17, 1998. 

Analysis of the contaminants in herring and in the seals at the end of the study revealed that PCBs accounted for the majority of Toxic Equivalents to 2,3,7,8-tetrachlo-rodibenzo-p-dioxin (TEQ). Combined with the pattern of immunotoxic effects at the level of the thymus and the T-cell, and a literature indicating an AhR-mediated immunotoxic vulnerability of the thymus [59, 60], the authors concluded that AhR-mediated effects, caused in large part by PCBs, led to the observed effects [57, 61]. They speculated that... 

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