George F. Solomon

Immunity, emotions and stress with special reference to the mechanisms of stress effects on the immune system.

Evidence from a variety of sources supports the notion that stress and emotional distress may relate to dysfunction and hypofunction of the immunologic system. We have experimental evidence that some forms of stress reduce primary and secondary antibody response to low dose antigen stimulation in rats and that adult immunologic responsivity may be altered by early infantile experience. Mixed-sex group housing at high male-female ratios increases severity of adjuvant-induced arthritis in the male rat. Graft-versus-host reactions are diminished by food-limitation stress to recipient animals. Sex segregated group-housed mice show larger murine virus-induced sarcomas when inoculated at 6 and 9 months of age than males housed individually with two or more females. Electric shock stress for 3 days prior to inoculation with virus reduces incidence and size of MSV tumors, while shock administered 3 days following inoculation increases tumor size. Female mice that develop spontaneous fighting behavior show significantly greater resistance to MSV tumors. Acutely ill schizophrenic patients with relatively high levels of IgA and IgG have a poorer short-term prognosis. Electrolytic lesions of the ventromedial and posterior nuclei of the hypothalamus of recipient and possibly also of donor animals impair the GVH reaction. Our experimental findings suggest that stress and central nervous system lesions affect thymus-derived lymphocytes (T-cells) and play a role in cell-cell interaction or the release of mediators from reacting lymphocytes. Ultimately, we may find that stress affects the macrophage, a hormone-sensitive cell that plays a role in afferent, central and efferent limbs of the immune system.

Stress, early experience and adjuvant-induced arthritis in the rat.

&NA; Group‐housing stress significantly increases the intensity of adjuvant‐induced arthritis in the male Fischer rat and can accelerate the time of maximal disease and rate of recovery. Handling in infancy does not alter disease in the adult animal. There are no significant differences in serum proteins, plasma adrenal corticosteroids or fibrinogen between stressed and nonstressed animals.

From the Symbolic Stimulus to the Pathophysiologic Response: Immune Mechanisms

Indirect evidence from a variety of sources, particularly clinical studies of emotional and stress factors in the onset and course of diseases associated with dysfunction or hypofunction of the immune system (infectious, allergic, autoimmune and neoplastic), support the notion that experiential factors can influence the functions of the immune system, presumably via neuroendocrine mediation. We dissect the immunologic system into its components in order to find identifiable targets within disease processes that are stress-responsive. The immune system can be divided into three limbs: afferent, comprising presentation of antigen; central, in which different classes of cells give rise to immune responses; and efferent, concerned with the sequelae of immunization. We must also consider sites in which the immune reaction occurs. We try to defend the assumption that emotional factors lead to small alterations in “immune balance” that can convert latent or mild illness to manifest or severe illness. We consider the interaction of specific components of the immune response with a variety of stress-responsive hormones and with cyclic AMP and cyclic GMP. We also speculate on the possibility of direct central nervous system influence on the immune response, particularly via the thymus which plays an endocrine role in immunologic competence. We outline a variety of influences hormones can play on specific components of each limb of the immune response. Since the interaction of neuroendocrine and immune systems no doubt involves an interplay of multiple mechanisms with multiple targets in the immune system, establishing and studying relationships within the entire matrix will be necessary. Evidence so far suggests that stress affects chiefly the efferent, and to some extent the afferent, limbs of the immune system and that macrophage activities are probably a major target.

THE RELATIONSHIP OF PERSONALITY TO THE PRESENCE OF RHEUMATOID FACTOR IN ASYMPTOMATIC RELATIVES OF PATIENTS WITH RHEUMATOID ARTHRITIS.

&NA; Two groups of asymptomatic female relatives of patients with rheumatoid arthritis were compared psychologically by means of the Minnesota Multiphasic Personality Inventory. The results indicated a greater incidence of emotional decompensation in those relatives lacking rheumatoid factor. It is speculated that emotional disturbance in conjunction with rheumatoid factor may lead to rheumatoid disease.

Emotions, stress, the central nervous system, and immunity.

Stress and emotional distress may influence the function of the immunologic system via central nervous system and possibly endocrine mediati0n.l Thus, environmental and psychologic factors might in some circumstances be implicated as aspects of the pathogenesis of cancer, the resistance to which growing evidence finds immunologic in nature, and of infections as well as of autoimmune diseases, which seem to have an association with states of relative immunologic incompetence. There are considerable data to link personality factors, stress, and, particularly, failure of psychologic defenses or adaptations to the onset and course of cancer and of infectious and autoimmune diseases, particularly rheumatoid arthritis. We are concerned especially with physiologic mechanisms, nervous and humoral, by which emotions and stress may relate to the diseases associated with dysfunction and hypofunction of the immunologic system. One possible link is the effect of stress-responsive adrenal cortical steroid hormones, which may be immunosuppressive. Stress effects on immunologic response might be expected to be observed under clinical conditions of gross failure of psychologic defenses, as generally occurs during acute mental illness. (However, in some forms of schizophrenic and depressive illnesses, the psychologic defenses may have “succeeded” in warding off psychic distress. Such patients do not show elevated adrenal cortical hormone levels.2) Abnormal central nervous system function in mental illness might be reflected immunologically; on the other hand, it is conceivable that abnormal immunologic factors may play a role in the pathogensis of mental illness, particularly schizophrenia, as suggested by FessePA and by Heath and, K r ~ p p . ~ The possibility that at least some forms of schizophrenia might be related to autoimmunity is intriguing in view of evidence to be presented that autoimmunity itself has emotional and stress antecedents.

Variation in Adrenal Cortical Hormones Within Physiologic Ranges, Stress and Interferon Production in Mice.

Summary Both stress and pharmacologic levels of adrenal cortical hormones have been reported to suppress the synthesis of interferon. We measured interferon in mice 6 hours after intravenous injection of NDV and related interferon titers to plasma corticosterone levels. The stress of repeated random electric shocks preceded by a warning buzzer during interferon production did not alter the response from that of controls; such stress administered for 5 hours prior to virus inoculation significantly enhanced interferon production. Administration of ACTH did not alter interferon response. Corticosterone administration adequate to produce high circulating steroid levels just greater than maximal attainable physiologic levels also did not alter response. All adrenalectomized mice had relatively higher interferon titers; however, neither prior stress nor partial corticosterone replacement therapy in any combination significantly altered interferon production. Administration of the virus itself produced an adrenal response in intact animals not subjected to other exogenous stress as great as that in animals subjected to exogenous stress prior or subsequent to injection of virus.

Personality correlates of the degree of functional incapacity of patients with physical disease

Abstract The paper reports an attempt to discover relationships between personality variables and the degree of functional incapacity shown by patients with rheumatoid arthritis. Two groups of patients were selected from a larger sample of female patients with rheumatoid arthritis. In the first group the stage of progression of the illness was less than the class of functional incapacity manifested by the patient; whereas, in the second group the stage of progression was either greater than or equal to the class of functional incapacity. A Minnesota Multiphasic Personality Inventory (MMPI) was administered to each patient, and a total of 88 personality scales derived from the items on this test were scored. An attempt was also made to estimate empirically what percentage of the MMPI scales would have shown significant differences between the groups by chance alone. The results indicated that the empirically derived average percentage of scales significantly differentiating two randomly selected groups was remarkably close to what would actually be expected on a priori grounds according to probability theory, and was much less than the actual percentage of scales which significantly differentiated the two groups actually utilized in the study. The patients with greater functional incapacity scored significantly higher on scales reflecting (1) physical symptoms; (2) depression, apathy and lack of motivation; (3) general ‘neurotic’ symptoms such as lack of ego strength, alienation and isolation from self and others, anxiety and hostility; (4) general ‘psychotic’ symptoms; (5) problems around control of impulses; and (6) particular personality traits, i.e. prejudice, ethnocentrism and dependency. The results were discussed with particular reference to previous work relating personality factors to the course of illness in multiple sclerosis, tuberculosis and cancer.

Peripheral Vasoconstriction Induced By Emotional Stress in Rats

a psychologic defense mechanism and that the development of arthritis often occurs after ego syntonic gratifications through muscular activity are blocked and the need for activity is frustrated. The development of peripheral rheumatoid arthritis in an extremely active patient after the occurrence of a myocardial infarct which drastically reduced his permissible activity level is a case in point. In his review of the literature Gardner’ states I that none of the various infective, chemical, immunologic and physical means tried has succeeded in experimentally inducing a condition

STRESS AND HORMONAL INTERVENTION IN THE GRAFT-VERSUS-HOST RESPONSE

That stress affects immune responses, generally by exerting a suppressive effect, has been well documented (1). We have shown such suppressive effects on antibody formation (2), and have also reported stress-induced increases in tumor size, which are probably a consequence of immunosuppression (3).

Psychoneuroimmunologic Aspects of Aging

Publisher Summary Immunosenescence might be defined as the alterations in immune function that occur to some degree in all older individuals and are distinguishable from immunodeficiency secondary to underlying disease, malnutrition, toxic exposure, or genetic disorder. Age-associated involution of the immune response is complex and heterogeneous. Immune senescence is characterized by lymphocyte dysregulation. Increased incidence of malignancy, infectious disease, autoimmune disorders, monoclonal gammopathies, and amyloidosis with age is felt to be linked with this decline of immunocompetence. The immunologic theory of aging proposes genetically programmed changes in immune cells as the determinant of maximum lifespan. The process of aging has been related to a complex variety of centrally “programmed,” hypothalamically mediated, metabolic and immunologic changes, in which psychological depression might be an involved variable in cause and effect roles. Immunosenescence is characterized by its high prevalence, interindividual variability, and complexity. The immune system is not uniformly affected by the aging process.