PRINCIPLES OF TOXICOLOGY - Biology East Borneo

10.8 SUMMARY 205The mainstay of treatment of multiple-chemical sensitivity involves avoidance of what are regardedas the inciting chemicals. In some cases, this can be taken to extremes, involving near isolation inspecially controlled environments. Vitamins and mineral supplements are often recommended, as wellas intravenous gammaglobulin, ostensibly to fortify the immune system. “Neutralization” doses ofextracts identified positively in provocation–neutralization tests are sometimes recommended to relieveor prevent symptoms. Reports of efficacy of these treatments are either anecdotal or from poorlycontrolled studies. Objective evidence that any of these treatments leads to improvement in the patient’scondition is generally considered to be absent.10.8 SUMMARYA fully functioning immune system is vital for defense against pathogenic microorganisms and toprevent the emergence of cancerous cells. It is a complex system, requiring the cooperation of manytypes of cells. The immune system is capable of both specific and nonspecific responses to insults.Specific responses are elicited by macromolecules recognized by the body as being foreign, termedantigens. The presence of an antigen can trigger a humoral response (i.e., the production of antibodiesthat bind rather specifically to that molecule) or a cell-mediated response in which cells carrying theantigen on their surface are attacked by specialized immune cells (e.g., natural-killer cells or cytotoxiclymphocytes).Drugs and chemicals can produce adverse health effects by influencing the immune system in oneof three ways:1. Causing a Hypersensitivity Reaction. There are four basic types of hypersensitivity reactions(types I–IV), each with a different mechanism. Depending on the type of reaction, symptoms may beimmediate or delayed, mild or severe, and involve different organs and tissues. Allergic reactions cancause considerable discomfort in the workplace, and some types (e.g., a severe type I reaction, oranaphylaxis) can be life-threatening.2. Suppressing the Immune System. Normal function of the immune system requires participationby many components, and disruption of any of these could conceivably result in impaired capability.If impairment is sufficient, the individual is at increased risk of infection and cancer. This has beenclearly demonstrated by patients on immunosuppressive therapy (e.g., transplant patients) and inanimal studies involving a variety of chemicals. Although there are few clear examples of immunosuppressionfrom occupational or environmental exposure in humans, there is no reason to expect thatthis effect cannot occur under these circumstances as well.3. Causing or Exacerbating Autoimmune Disease. By producing a dysregulation of the immunesystem, drugs and chemicals are capable of causing the immune system to attack normal bodyconstituents. This has been clearly demonstrated for several drugs, and a number of reports suggestthat it may also occur from occupational and environmental exposures.The potential for a chemical to produce immunotoxicity can be assessed through a variety of in vivoand in vitro tests. Most of these tests focus on effects on a very specific aspect of the immune system.The immune system possesses considerable functional redundancy and extra capacity, and alterations(or “abnormalities”) in one or a few parameters may not necessarily result in diminished overallfunctional of the immune system. Consequently, the results of these tests must be interpreted carefully.REFERENCES AND SUGGESTED READINGBurleson, G. R., J. H. Dean, and A. E. Munson, Methods in Immunotoxicology, Wiley-Liss, New York (1995).