Book Review

Psychoneuroimmunology

N Engl J Med 1993; 328:1133-1134April 15, 1993

Article

Psychoneuroimmunology
Second edition. Edited by Robert Ader, David L. Felten, and Nicholas Cohen. 1218 pp., illustrated. San Diego, Calif., Academic Press, 1991. $129.95. ISBN: 0-12-043782-1

If an artificial rose is placed before a subject who has an allergy to the flower, a “rose cold” may be provoked. In other words, suggestion can elicit the entire immune reaction of allergic rhinitis in certain patients. Asthma, hay fever, and a variety of other hypersensitivity responses may be similarly precipitated. The hybrid discipline of psychoneuroimmunology has emerged from such clinical observations, and from a growing awareness of the links between the immune and neuroendocrine systems. Bidirectional communication between nervous and immune networks might explain not only curiosities like the “rose cold” but also how behavior and stress affect immunity and, conversely, how immune processes might affect behavior. The extent of such relations and their clinical relevance have not been firmly established, but the data are so suggestive that certain tantalizing speculations may be entertained.

Psychoneuroimmunology is an encyclopedic, multiauthored anthology that is now the single best source on this highly complex interdisciplinary subject. The book, over 1100 pages of text, is divided into sections that define the neurochemical links between the nervous and immune systems (i.e., the production and recognition of neuropeptides by immunocytes); describe their functional interactions (in the effects of various hormones on immune function); discuss the influence of behavior on immunity (for example, the influence of conditioning on immune responses); and finally, offer clinical data on the effects of such psychosocial factors as stress and disease on immunity. Ranging from the immune responsiveness of medical students under stress to the genetic and protein structure of various neurotransmitter receptors, Psychoneuroimmunology appeals to an eclectic audience. It does so with scholastic rigor, helpful diagrams and figures, exhaustive referencing (over 4400 listings), and uniform organization despite its more than 80 contributors. There is some overlap of subject matter, but the editors have generally welded the various components into a cohesive presentation.

The central tenet of this book is that the immune system is entwined with the neuroendocrine system. One might visualize at the points of a triangle the three systems, with bidirectional pathways connecting each pair of them. The immune system has multiple receptors for neurotransmitters and hormones; various immunocytes synthesize mediators first identified from neuroendocrine sources; and lymphokines and certain complement proteins affect neurologic function. In turn, neuroendocrine hormones and autonomic pathways directly affect thymus and bone marrow function and modulate the behavior of macrophages and lymphocytes. These and other observations -- from molecular biologic probes to Pavlovian conditioning and Penfield-like anatomical-correlation studies -- are beginning to reveal the outlines of a highly integrated cognitive system, whose modalities of perception extend across the barriers we have artificially created.

Beyond the biochemical connections, the data for such links are anatomical (the immune system is innervated), ontogenetic (part of the thymus derives from neurocrest ectoderm), and phylogenetic. The last is, curiously, not considered in the book and represents a serious omission. Jesse Roth and coworkers present a compelling hypothesis that communicative substances have a long phylogenetic history, since unicellular organisms contain molecules resembling the messenger peptides of vertebrates. They argue that many hormones and their receptors originated with microbes and that, later in evolution, anatomical and functional diversity led to the neuroendocrine and immune systems. This so-called paleocentric or unification theory would predict that a hormone may be synthesized not only in the specialized tissue, but also by other cell types (for example, corticotropin and endorphins are normally produced in seven different tissues).

Two factors color our thinking about interconnections of the immune and nervous systems. The first is the unfortunate duality of the mind-body problem in our culture, in which psychically based alternative medical remedies are advocated for everything from allergies to warts. These so-called mind-over-matter practices are anathema to orthodox biomedicine, and thus the very term “psychoneuroimmunology” conjures up quackery. The second factor is the segregation of disciplines, methods, and original research concerns -- that is, their separate historical development. Because neurotransmitters such as substance P and vasoactive intestinal peptide were first discovered as neuroendocrine mediators, we must now reconsider the meaning of their “shared” role in immune trafficking; in fact, it is not at all clear to which system they belong.

Although psychoneuroimmunology has established its scientific foundation, the editors shy away from extending the scope of the field to its next tentative stage. It is precisely at the intersection of the intellectual foundations of immunology and the neurosciences that the definition of the self may be approached and, thus, the excitement of a scientific discipline focused on such questions. But the most important omission in the book is the absence of a broad-based debate that goes beyond the phenomena to a true epistemology. The collaboration of cognitive scientists and immunologists has already generated research programs and interesting modeling (such as that described in Theoretical Immunology, edited by A.S. Perelson [Redwood City, Calif.: Addison-Wesley, 1988]), but this level of inquiry has been ignored here.

There seem to be too few instances in biomedicine in which the vector of current interest is reversed from defining ever smaller parts to constructing wholes. Psychoneuroimmunology now affords an opportunity to establish how our cognitive system -- composed of nervous, endocrine, and immune constituents -- functions. Seeking conceptual similarities and holistic design must remain a focus of this developing discipline. If it takes another 10 years to prepare the next edition, the editors of Psychoneuroimmunology will probably require several volumes to encompass the results of the current explosive interest, as well as to represent the more tentative areas requiring attention. They have consciously avoided forays into the realms of cognitive science and theoretical modeling. But that is probably where the most productive hypothesizing will occur, and the science will ideally follow. Cross-disciplinary scientists must be trained for that endeavor, and this book is a good place to start.

Alfred I. Tauber, M.D.
Boston University School of Medicine, Boston, MA 02118