Abstract
It was with great pleasure that I was invited to review the new, and much needed, comprehensive summary of immunotoxicology edited by Helen Tryphonas and her colleagues. The book is divided into seven sections, and will be reviewed here using this format.
Section I is the weakest part of the book. The authors make, what I believe, is a fundamental error common in immunotoxicology reviews. They attempt, in nine pages of text, to provide an overview of immunology for the reader. Simply put, this is not a useful exercise. The editors should assume that (1) the reader will have a working knowledge of the fundamentals of immunology or (2) if not, this cannot be remedied in nine pages of text. This is not a specific criticism of the editors or authors. This is a problem common to immunotoxicologists. We assume that immunology is an arcane subject that needs to be explained at some basic level to readers of what is an otherwise extensive and challenging work. Nowhere in the text do you find an extensive glossary of terms, such as a list of interleukins and the functions associated with them. This would be much more useful to the general toxicologist than a short description of the immune system and what it does. This is really the only part of the book with which I have any issue, and it is not something unique to this text.
Section II is the strongest part of the book—an extensive and very educational review of ecotoxicology and the uses of immunological parameters within this field. I cannot think of a review of immunoecotoxicology comparable to that assembled by the editors. There are a number of strengths to this section. First, it introduces the reader to the evolution of innate and specific immunity. This isn’t accomplished in one dedicated chapter; rather, taken as a whole, it provides the reader with an understanding of the primitive forms of immunity observed in nematodes, mollusks, and other phyla, which is likely to be unfamiliar territory to many immunotoxicologists as well as specialists in other areas. Secondly, the section provides a useful guide as to how immune parameters can be used to assess environmental contamination, and in particular, the advantages of such sentinel species as oysters, frogs, and fish in detecting the adverse effects of xenobiotics. Finally, there are very instructive discussions of the actual adverse effects of xenobiotic exposure to immune function, particularly in marine mammals. Although to a certain extent this is a controversial area, the authors of chapters on reptiles, amphibians, and other wildlife should be credited with putting forward important data supporting the idea that immunotoxic effects of xenobiotic exposure is an area of concern worthy of more research and supportive of attempts at environmental remediation and pollution control.
Section III deals with a much more difficult area of inquiry—immunotoxicity in humans and the relevance of animal models to human health. This is not unique to immunotoxicology. As a professional who constantly deals with translating findings in nonclinical toxicology studies to adverse effects in humans, I certainly sympathize with the issues the authors of the chapters in this section must deal with. Taken as a whole, this section demonstrates the lack of cooperation and communication between immunotoxicologists and clinical medicine. Most of the examples of relevance to human health are derived either from epidemiological studies which can almost always be criticized on methodological grounds, deal with such issues as transplantation medicine where, frankly, immunotoxicology studies have not been particularly useful in discovering what couldn’t be anticipated based on drug pharmacodynamics, or attempts to correlate extent of effects observed in animal studies with risk to human health. The authors of these chapters are to be complemented on the extent of data discussed, and they have made some very good points about what is needed to understand the relevance of laboratory findings to human health, but they nevertheless are dealing with what is a difficult issue in immunotoxicology (when taken to mean unintended immunosuppression): lack of a smoking gun. That is, I know of no situation in immunotoxicology (exclusive of drug allergy and autoimmunity, to be discussed below) comparable to thalidomide and birth defects or troglitazone and catastrophic liver failure. These are the types of findings that would, in a sense, validate the efforts of immunotoxicologists. This section does contain some useful discussion of such subjects as developmental immunotoxicology, immunohistopathology, and use of nonrodent models.
Sections IV and V address issues that are important in clinical medicine—chemically induced immune-mediated hypersensitivity, food allergy, and autoimmunity. The length of these sections is somewhat out of proportion to the extent of the problems. But there is a reason for this, and the chapters demonstrate this: much is unpredictable based on available methodology and much more research is needed. This section contains very valuable discussions on what is known about xenobiotic-induced allergy and related phenomena, and is well written. However, there is an overall theme to these sections—are we looking at the wrong places in immunotoxicology? That is, we have well-developed methodologies for unintended immunosuppression (and, as Section II shows quite well, these can be very useful and provide important and relevant data), but this seems to be, at least based on available information, a less important issue as compared to immune-mediated hypersensitivity and related problems. This imbalance needs to be addressed. Finally, a minor comment. Overall, the editors did a fine job with this large text. However, a discussion of guinea pig models is included in the chapter on “Hypersensitivity Reactions: Nonrodent Animal Models.” The text is both somewhat redundant (the same issues with the guinea pig models are discussed to some extent in the prior chapter) and the taxonomic implications should have been considered.
Sections VI and VII are useful primarily in pointing out the areas where immunotoxicology can grow. Clearly, areas such as genomics, proteomics, risk assessment and management are the future of the science and inclusion of discussions about these areas is an important addition. The discussion of biomarkers is particularly important. These are the tools that make laboratory investigation relevant to the world we live in. My only critical comment is that there is the obligatory chapter on statistical analysis. Once again, it is an important area, but probably does not add a great deal to the value of the book, simply because it’s too brief. The editors should assume that much of the discussion in this section should already be familiar to the reader, and, if not, there are other sources which provide much more information.
In conclusion, this is an excellent overview of the science of immunotoxicology and I would recommend this to anyone as an educational resource. It does not, however, replace such works as Burleson, Dean, and Munson’s Methods in Immunotoxicology or other important “how to” texts. It is an intelligent and important summary of the field and the editors and authors are to be congratulated.