John Sheridan, PhD, David Padgett, PhD, and Ning Quan, PhD, develop animal models for studying effects of stress on the immune system. These models are used to examine mechanisms by which activation of neuroendocrine pathways intersect and regulate inflammatory and immune responses. Rodent models have been developed to examine the effects of stress in three research areas: susceptibility to microbial infections; tissue repair/wound healing; and immune system/cytokine signaling to the central nervous system across the blood brain barrier. These models are used in parallel with human studies performed by other members of the IBMR.
 Phillip Popovich, PhD, and Caroline Whitacre, PhD, use cellular and molecular approaches to determine how spinal cord injury (SCI) influences the ability of immune cells to function at the injury site and in tissues throughout the body. Virginia Sanders, PhD, has shown that lymphocyte activity is dramatically influenced by catecholamines – the chemical messengers of the sympathetic nervous system (SNS). For example, efficient production of antibodies by B cells requires that catecholamines bind to the beta2-adrenergic receptor found on B cells and a subset of T cells. Studies between Sanders and Popovich are determining whether antibody production in SCI individuals is negatively affected by disruption of SNS function. Sanders’ work also has relevance in diseases like multiple sclerosis – the area of research emphasis in Whitacre’s laboratory. Multiple sclerosis is an autoimmune disease of the brain and spinal cord caused by overactive T- and B-lymphocytes. Recent work from Whitacre’s laboratory has focused on how gender and pregnancy influence the neurodestructive capacity of autoreactive T cells.
Notable findings of Barbara Andersen, PhD, published in the journal Cancer, stemmed from an ongoing clinical trial studying women with breast cancer recurrence. Women with stage II/III breast cancer were initially assessed following diagnosis/surgery and prior to adjuvant therapy. Then they were reassessed every six months. Eight years into the trial, cancer had recurred in 30 patients assessed after receiving their second diagnosis. Their data (the R group) were compared to a sample of trial patients with no evidence of disease (disease free, or DF). As hypothesized, patients’ cancer-specific stress at recurrence was higher than stress levels for the DF group at the equivalent time. Importantly, the R group reported stress for recurrent diagnosis equivalent to that reported for their initial diagnosis. Identical results were found for measures of health status and symptomatology. In contrast, analyses for emotional distress and social functioning showed no pattern of disruption for the R group at recurrence and levels equivalent to those of the DF group. This was the first controlled prospective psychological analysis of patient response to recurrence. Patient stress is “compartmentalized” and does not, at least in the early weeks, result in diffuse emotional distress and quality of life disruption, underscoring the resilience of patients facing recurrence.
Courtney DeVries, PhD, Immunology and Stress Program, developed a mouse model of cardiac arrest and cardiopulmonary resuscitation, and showed that cardiac arrest with CPR increases subsequent anxiety-like behavior and decreases social interaction. Her group also reported sex differences in recovery from focal ischemia, as well as social facilitation of wound healing. The team of Randy Nelson, PhD, showed that exogenous pyruvate prevents stress-evoked suppression of mitogen-stimulated proliferation. They also showed that pyruvate works by affecting the pattern of glucocorticoid secretion. Pyruvate could have clinical value in treating the effects of stress in immunocompromised individuals, such as AIDS patients. In addition, Nelson reported that social environment modulates seasonal immune responses in mice. Ongoing Research Program
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Human Psychoneuroimmunology (PNI) Program – This program involves: Barbara Andersen, PhD, Psychology; Charles Emery, PhD, Psychology; Ronald Glaser, PhD, Molecular Virology, Immunology and Medical Genetics; Janice Kiecolt-Glaser, PhD, Psychiatry; Stanley Lemeshow, PhD, College of Public Health; William Malarkey, MD, Internal Medicine; and Eric Yang, PhD, Molecular Virology, Immunology and Medical Genetics. The program focuses on psychological stressors and behavioral questions that could affect health by modulating the immune and endocrine systems. One recent focus is on how chronic stressors, such as caregiving, and acute stressors, such as marital conflict, substantially enhance production of proinflammatory cytokines linked with age-associated diseases, providing a window on how stress contributes to morbidity and mortality. A program exploring the role that stress may play in skin cancer has developed into a well-funded research program. These studies will expand to include breast cancer survivors in collaboration with the Cancer Control Program in Ohio State’s Comprehensive Cancer Center.
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Biobehavioral Aspects of Stress and Cancer Program – Cancer survivors are the focus of work spearheaded by Janice Kiecolt-Glaser, PhD, Ronald Glaser, PhD, Electra Paskett, PhD, MSPH, and William Malarkey, MD. One project funded by the National Cancer Institute addresses the role that proinflammatory cytokines play in combination with depression among breast cancer survivors who experience debilitating fatigue, and the ability of a yoga intervention to modulate endocrine and immune responses. Barbara Andersen, PhD, Psychology, has examined biobehavioral aspects of cancer to learn whether reducing stress and changing health habits have a significant impact on cancer recurrence and survival.
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Comparative Medicine/Animal Model Program – This group involves Michael Bailey, PhD, David Padgett, PhD, John Sheridan, PhD, Ning Quan, PhD, all in the Oral Biology, as well as Jon Godbout, PhD, Molecular Virology, Immunology and Medical Genetics. They focus on developing animal models for psychoneuroimmunology research that models the studies with human subjects. • Behavioral Immunology and Stress Program – The research group of Courtney DeVries, PhD, and Randy Nelson, PhD, Psychology, studies the effects of stressors on inflammation after stroke or cardiac arrest, as well as seasonality in immune function, disease and mortality.
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Neuroimmunology Program – Jon Godbout, PhD, Phillip Popovich, PhD, Virginia Sanders, PhD, and Caroline Whitacre, PhD, are investigators in Molecular Virology, Immunology and Medical Genetics whose research focuses on diverse yet interrelated areas of neuroimmunology.
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Neuroendocrinology Program – William Malarkey, MD, and Jeanette Webster Marketon, PhD, are investigators in Internal Medicine who focus on neuroendocrinology in a clinical setting and at the molecular level.
Research Highlights of 2006
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Comparative Medicine/Animal Model Program – To study the effects of stress on the immune system, Michael Bailey, PhD, Jon Godbout, PhD, David Padgett, PhD, John Sheridan, PhD, and Ning Quan, PhD, develop animal models and use them to examine mechanisms by which activation of neuroendocrine pathways intersect and regulate inflammatory and immune responses. Rodent models have been developed to examine the effects of stress in three research areas: susceptibility to microbial infections; tissue repair/wound healing; and immune system/cytokine signaling to the central nervous system across the blood brain barrier. These models are used in parallel with human studies performed by other members of the IBMR.
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Neuroimmunology Program – Phillip Popovich, PhD, and Caroline Whitacre, PhD, use cellular and molecular approaches to determine how spinal cord injury (SCI) influences the ability of immune cells to function both at the site of injury and in tissues throughout the body. The work of Virginia Sanders, PhD, has shown that lymphocyte activity is dramatically influenced by catecholamines – the chemical messengers of the sympathetic nervous system (SNS). For example, efficient production of antibodies by B cells requires that catecholamines bind to the beta2- adrenergic receptor found on B cells and a subset of T cells. Studies between Sanders and Popovich are determining whether antibody production in SCI individuals is negatively affected due to disruption of SNS function. Sanders’ and Whitacre’s work also has relevance for diseases such as multiple sclerosis, an autoimmune disease of the brain and spinal cord caused by overactive T and B lymphocytes. Recent work in Whitacre’s lab, which focuses on multiple sclerosis, examines how gender and pregnancy influence the neurodestructive capacity of autoreactive T cells. Sanders, Popovich, Daniel Ankeny, PhD, and co-workers have shown that experimental spinal cord injury elicits chronic activation of a B cell-dependent autoimmune response. In this study, high levels of anti-DNA antibodies were detected in spinalcord- injured rats with a pattern that is similar to that seen in systemic lupus erythematosus. This is the first report that spinal cord injury can cause a clear dysregulation of B-cell function.
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Behavioral Immunology and Stress Program – Courtney DeVries, PhD, developed a mouse model of cardiac arrest and cardiopulmonary resuscitation (CPR) and showed that cardiac arrest with CPR increases subsequent anxiety-like behavior and decreases social interaction. Her group also reported sex differences in recovery from focal ischemia, as well as social facilitation of wound healing. The research group of Randy Nelson, PhD, showed that prenatal day length influences immune function in adulthood. These findings might explain season of birth as a risk factor in several diseases. His group also showed the existence of trade-offs between cutaneous immune responses. In addition, Nelson reported that social environment modulates seasonal immune responses in mice.
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Neuroendocrinology Program – William Malarkey, MD, investigates toxic stress and the biology of chronic inflammation, the precursor to chronic pain and most of the diseases of aging, including arthritis, cancer and cardiovascular disease. Work in progress or soon to begin includes studies on obesity, chronic stress and inflammation, and stress-reduction strategies for treating chronic inflammation. Jeanette Webster Marketon, PhD, uses molecular approaches to determine how factors such as disease status or infection modulate glucocorticoid receptor signaling. Glucocorticoid receptors are essential for life, and impaired signaling through this receptor is involved in many autoimmune/inflammatory diseases.
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Human Psychoneuroimmunology Program – A recent study by Janice Kiecolt-Glaser, PhD, Ronald Glaser, PhD, Stanley Lemeshow, PhD, and others showed that dietary intake of omega-3 fatty acids may interact with depression to fuel inflammation. The cross-sectional study has provided the basis for two new funded omega-3 randomized controlled trials.
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