Immune response, agents affecting

Awareness of immunotoxicology was stimulated by a comprehensive review by Vos in 1977, in which he provided evidence that a broad spectrum of xenobiotics alter immune responses in laboratory animals and subsequently may affect the health of exposed individuals. Several additional reviews, as well as national and international scientific meetings, have reinforced these early observations. In several studies, alteration of immune function was accompanied by increased susceptibility to challenge with infectious agents or transplantable tumor cells, indicating the resulting immune dysfunction in altered host resistance. Clinical studies in humans exposed to xenobiotics have confirmed the parallelism with immune dysfunction observed in rodents. The latter sections in this volume describe studies with xenobiotics that resulted in immune modulation in rodents and man. 

Because of the autoimmune basis of rheumatoid arthritis, various other drugs that affect the immune response are used on a limited basis. For instance, cyclosporine (Sandimmune), an immunosuppressant agent that is used to prevent rejection of organ transplants (see Chapter 37), is sometimes used to treat... 

Data are available for acute and intermediate inhalation exposures that resulted in death of animals. For the most part, these exposures also affected the respiratory tract and the immune response to bacterial agents. An intermediate inhalation exposure study of rats prior to mating and during pregnancy did not result in fetotoxic or teratogenic effects. Limited information is available regarding chronic inhalation exposure. 

Benzene also affects functional immune responses, as indicated by decreased resistance to infectious agents. Pre-exposure to benzene at >30 ppm for 5-12 days increased the bacterial counts in mice on day 4 of infection with Listeria monocytogenes (Rosenthal and Snyder 1985). Recovery of the immune system was noted on day 7. The effects did not occur at 10 ppm. In addition, a concentration-dependent statistically significant depression was noted in T- and B-lymphocyte populations from day 1 through day 7 at 30 ppm and above. B-cells were more sensitive to benzene than were T-cells on a percentage-of-control basis. This indicates a benzene-induced delay in immune response to L. monocytogenes. Concentrations of 200 or 400 ppm for 4-5 weeks (5 days per week) suppressed the primary antibody response to tetanus toxin in mice, but there was no effect at 50 ppm (Stoner et al. 1981). In another intermediate-duration exposure study, no changes were noted in the numbers of splenic B-cells, T-cells, or... 

The effects of marijuana on immune function have been reviewed (122). The studies suggest that marijuana affects immune cell function of T and B lymphocytes, natural killer cells, and macrophages. In addition, cannabis appears to modulate host resistance, especially the secondary immune response to various infectious agents, both viral and bacterial. Lastly, marijuana may also affect the cytokine network, influencing the production and function of acute-phase and immune cytokines and modulating network cells, such as macrophages and T helper cells. Under some conditions, marijuana may be immunomodulatory and promote disease. 

With the discovery and development of cyclosporine, a new era in immunopharmacology was born. Cyclosporine was the first agent to affect a specific cell line of the body s immune defenses. It is suppressive mainly to T cells, in condast to the cytotoxic agents, which affect all cell lines at the same time. Cyclosporine is the forerunner of a group of immunosuppressants that are acdve against specific components of the immune response. 

The innate immune response, which is nonspecific, displays no time lag in responsiveness, and is not intrinsically affected by prior contact with infectious agent. 

Flavonoids affect the immune system and the body s inflammatory cells. This function is partly accomplished through the effects on enzymes involved in the immune response and the generation of inflammatory cells. Balentine et al. (1999) recently reported that only the aglycon cyanidin, not the anthocyanin glycoside, showed inhibitory effects on enzymes involved in inflammatory activity. The anthocyanins can be metabolized into their glycoside-free constituents either before or after absorption in the gut and may thereby act as anti-inflammatory agents in the body. Middleton and Kandaswami (1994) stress the fact, however, that as most of these studies have been carried out as in vitro experiments, care should be taken not to draw too extensive conclusions for the in vivo actions of flavonoids. Fundamental biochemical research is needed before the mechanisms behind the diverse actions of flavonoids are fully understood. 

Antidotes are available for some Toxins and others are being developed. However, many Toxins affect such basic biochemical mechanisms within the body that potential antidotes often have severe debilitating or toxic side effects. Unlike chemical agents. Toxins can cause an immune response. Vaccines are available for some Toxins but generally require 4 to 15 weeks for the body to produce antibodies. Passive immunotherapy is effective for some neurotoxins but must be instituted shortly after exposure. 

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