Psychoneuroimmunology, Stress, and Infection

Herman Friedman, Thomas W. Klein, Andrea L. Friedman

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000722550
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

Psychoneuroimmunology is the emerging science devoted to studying the two-way relationship between the nervous and immune systems. Psychoneuroimmunology, Stress, and Infection highlights the latest information concerning microbial infections in both man and animals as related to stress and especially stress hormones.
The volume focuses on psychoneuroimmunology as it impacts the immune system in general and also the relationship between neurological events which influence susceptibility and/or resistance to infectious agents such as bacteria, fungi and viruses, as well as parasites. Prominent researchers describe the involvement of the hypothalamus-pituitary-adrenal (HPA) axis on immunity as a function of the nervous system. The text discusses hormones such as prolactin and growth hormone and steroid induced susceptibility to infection and neuropeptides, including vasoactive intestinal peptide, and substance P. The effects of catacholamines on immunity and susceptibility to infection are also covered. This reference also details the involvement of immune cells in the synthesis of neuropeptides, including hormones and endorphins, their effect on the brain as well as the effects of interleukins and tumor necrosis factor on the central nervous system. The book concludes with an interesting look at the relationship between aging, psychoneuroimmunology, and infection.
Although there is much new knowledge concerning the nature and mechanism of immune responses, including the mediators involved, Psychoneuroimmunology, Stress, and Infection also presents important discussions and reviews that are long overdue and provide a major contribution to the area of biomedical knowledge in general and psychoneuroimmunology in particular.

Chapter 1

HISTORICAL PERSPECTIVES ON PSYCHONEUROIMMUNOLOGY

Robert Ader

Center for Psychoneuroimmunology Research
Department of Psychiatry
University of Rochester School of Medicine and Dentistry
Rochester, NY

Psychoneuroimmunology refers, most simply, to the study of the interactions among behavioral, neural and endocrine (or neuroendocrine), and immunological processes of adaptation. Its central premise is that homeostasis is an integrated process involving interactions among the nervous, endocrine and immune systems. The term was first used in 1980, in my presidential address to the American Psychosomatic Society.¹ Its most conspicuous use was as the title of an edited volume² which one reviewer referred to prophetically as “The signature volume of a new field of research.” This first volume was an attempt to bring together emerging research suggesting a relationship between the brain and the immune system. Traditionally, however, the immune system has been considered an autonomous agency of defense - a system of bodily defenses regulated by cellular interactions that are independent of neural influences. Besides, there were no known connections between the brain and the immune system. To be sure, it was known that hormones or at least adrenal hormones could influence immunity; some investigators were aware that brain lesions could influence immune responses; and it was also known or, at least, suspected that emotional states were associated with the development or progression of diseases related to the immune system. Few scientists at that time, however, took such observations too seriously. After all, there were no mechanistic explanations for how such things could happen.

Considering the brief time during which multidisciplinary research has addressed brain-immune system interactions, a great deal of data has accumulated in support of the proposition that homeostatic mechanisms are the product of an integrated system of defenses of which the immune system is one component.³ Autonomic nervous system activity and neuroendocrine outflow via the pituitary can influence immune function, and cytokines and hormones released by an activated immune system can influence neural and endocrine processes. Regulatory peptides and receptors once confined to the brain are expressed by both the nervous and immune systems and each system is thereby capable of modulating the activities of the other. It is hardly surprising, then, to find that immunologic reactivity can be modified by Pavlovian conditioning - or that the behavioral and emotional states that accompany the perception of and the effort to adapt to events in the real world can influence immune responses. Thus, psychoneuroimmunology successfully challenged the commonly held assumption of an autonomous immune system. One may, therefore, entertain the proposition that changes in immune function mediate the effects of psychosocial factors and stressful life experiences on the susceptibility to and/or the precipitation or progression of some disease processes.

It is not my intent, in this introductory chapter, to review the literature outlining the history of psychoneuroimmunology. I have, instead, taken my charge literally and chosen the more manageable task of presenting here some editorial comments and some historical perspectives on psychoneuroimmunology. These are, of necessity, brief and selected and only cover developments up until about 1980. Very much more could be written about the people and the findings described here because these are rich personal stories. Much more could also be written about what was contemporary and what came before and what came after the 1970s, but this is a chapter - not a book. The research I have chosen to highlight was not necessarily even the first of its kind; in my opinion, however, the systematic research initiated during the 1970s was “the right stuff at the right time.” No one study can be said to have been (or could have been) responsible for psychoneuroimmunology. I suspect that none of the research initiatives described below would have had quite the same impact had it not been for the converging evidence of brain-immune system interactions being provided by the others at about the same time. Studies of brain-immune system relationships had been appearing in the literature for many, many years. However, it was the coalescence of research initiated during the 1970s and sustained thereafter - and the identity provided by the label, psychoneuroimmunology, itself - that reawakened long-standing interests and attracted new investigators into this “new” field.

The notion of integration is neither new nor, for the most part, can it be considered controversial. It was David Hamburg, I think, who pointed out that biochemistry, a hybrid discipline, was initially viewed as a combination of poor biology and weak chemistry. Today, it is basic and central to the study of medicine. Psychopharmacology is a recognition of the fact that drug effects depend to a large extent on the state of the organism into whom they are introduced. Neuroendocrinology reflects an appreciation of the fact that the functions of the endocrine system can not be fully understood without reference to its interactions with the nervous system. And psychoneuroendocrinology acknowledges that the feedback and feed forward pathways between these “systems” influence and are influenced by behavior. Hybrid disciplines are not always or solely attempts at integration or synthesis. Basic fields such as neurochemistry or immunopharmacology, and clinical subspecialties such as neuropsychiatry, for example, designate a focus within a parent “discipline.” In fact, in keeping with the zeitgeist of the biomedical model, the latter reductionistic referent is probably the more common one.

Among other shortcomings, disciplinary boundaries tend to keep insiders in and outsiders out. Hybrid disciplines have nevertheless emerged and significantly extended our understanding of the functions of the components of interacting systems. Why is it, then, that psychoneuroimmunology precipitated - and, in some circles, continues to engender so much resistance and enmity? Certainly, the attention that psychoneuroimmunology has captured in the popular press and its exploitation by those who redefine and use psychoneuroimmunology as the scientific umbrella for their own undisciplined and untested theories and practices cannot have endeared psychoneuroimmunology or investigators who study brain-immune system interactions to the remainder of the scientific community. In my unsubstantiated view, however, the reasons lie as much within as without the biomedical community. Some scientists are willing to say they “don’t believe” there’s anything of substance in psychoneuroimmunology, although they are not necessarily willing to be quoted. Of course, scientists do not have recourse to “I don’t believe it” as grounds for rejecting hypotheses. One can argue, “I don’t believe it because…” as in: “I don’t believe it because there are no connections between the brain and the immune system.” Such arguments are capable of disproof and, with respect to psychoneuroimmunology, all such arguments have been contradicted by experimental data. Unfortunately for the development of the field, however, there are those in influential positions who, purportedly, believed that psychoneuroimmunology would go nowhere and acted in a consultative capacity on this “belief.” There is, too, a sense of unease among some so called “hard” scientists who seem to view the scientific study of behavior as an oxymoron. In truth, the sophistication in experimental design and analysis of research by the behavioral sciences far exceeds that of the more classical biomedical sciences and even molecular biology, and is essential for addressing the quantitative questions (e.g., when, how much, under what conditions) that are raised by factoring behavioral, neural and endocrine variables into the experimental analysis of immunoregulatory processes.

Within the field, there have been some minor battles over “turf”, but none has altered the defining theme of the field. The emergence of psychoneuroimmunology has actually broadened some fields of study that were more narrowly defined in the recent past (e.g., papers in psychoneuroimmunology are now solicited for publication in the Journal of Neuroimmunology). “Neuroimmunomodulation” and “neuroendocrinimmunology,” mere mispronunciations of psychoneuroimmunology, seem to have been precipitated to disengage from the study of behavior and/or to more specifically brand the field with one’s own personal or disciplinary irons. Neither label changed the substance of the interdisciplinary research it promoted. (Of course, if you can come up with still another name, you, too, can also come up with another “First Conference on….”)

The first sustained program of research were the studies of Russian investigators on the classical conditioning of immune responses. This research, derived from a Pavlovian perspective, began with Metal’nikoff and Chorine⁴ who were working at the Pasteur Institute in Paris. This research was reviewed in English in 1933 by no less than Clark Hull,⁵ a renowned learning theorist of that era. It was also reviewed in 1933 and, again, in 1941 by Kopeloff.^6,7 The only other substantive review of this literature in English appeared in Psychoneuroimmunology.⁸ None of these early reviews attracted much attention or had any impact on research outside the then Soviet Union, including the studies of brain lesions on immune reactions and the physiologic studies of stress derived from the work of Hans Selye. Even the research implicating the nervous system in the modulation of immune responses initiated by Rasmussen and his colleagues and others in the 1950s and 60s failed to attract much sustained attention from any but a few behavioral scientists.

Aaron Frederick Rasmussen, Jr. was certainly one of the earliest pioneers of psychoneuroimmunology. His association with Norman Brill, then Chair of the Department of Psychiatry at the UCLA School of Medicine, was probably the first collaboration between a microbiologist/immunologist and a behavioral scientist. Rasmussen died in 1984, at the age of 68, after serving as Chair of the Department of Medical Microbiology and Immunology (1962–1969) and thereafter as Associate Dean of the School of Medicine. He is remembered as a beloved and inspiring teacher and colleague and an outstanding virologist whose genetic studies laid the foundation for understanding the notorious worldwide variability in influenza viruses. Rasmussen was a meticulous experimental microbiologist, who, at the same time, never lost site of host factors in disease. He was intrigued by the unproved conventional wisdom that emotional states influence the course of infectious illness, as depicted by such great novelists as Thomas Mann and as observed by such great pre-modern clinicians as Sir William Osler. An integrative thinker not bound by disciplinary lines, Rasmussen sought out Brill to discuss his “psychomicrobiological” ideas.

In 1957, Rasmussen, Marsh and Brill demonstrated that a stressful experience, avoidance conditioning, could increase the susceptibility of mice to herpes simplex virus. In a series of landmark papers, the pathogenic effect of emotional stress on animals exposed to herpes virus,⁹ Coxsackie B virus,¹⁰ and vesicular stomatitis virus¹¹ was explored. He and his coworkers also found decreased susceptibility to poliomyelitis virus in stressed monkeys, an early demonstration of the variability in stress effects on disease susceptibility.¹² Anticipating modern work in psycho-oncology as well as psychoneuroimmunol...