Journal of Advanced Nursing, 1996, 23, 657-664 Psychoneuroimmunology: an emerging framework for nursing research Jamce M Zeller PhD RN FAAN Professor, Department of Medical Nursing and Associate Professor, Department of Immunology Microbiology, Rush-Presbytenan-St Luke's Medical Center, Chicago, Minos Nancy L McCain DSN RN “Associate Professor, School of Nursing, Virgnsa Commonwealth University, Richmond, Virgina and Barbara Swanson DNSc RN ‘Study Coordinator, Women’s Interagency HIV Study, Unwversty of lino at Chicago, (Chucago, nos, USA Accepted for pubucanon 27 May 198 ZELLER] M, McCAINN L & SWANSON 8 (1996) Journal of Advanced Nursing 23, 657-664 Psychoneuroimmunology. an emerging framework for nursing research Psychoneuroimmunology (PNI) 1s concerned with the mechanisms of bidirectional communication between the neuroendocrine and immune systoms Investigators in other disciplines have used this framework to guide the examination of possible relationships between behavioural factors and the progression of rmmunologically mediated 1llnesses and to evaluate the role of immune products in central nervous system disturbances Nurse scientists have fan opportunity to make unique contnbutions to the growing field of PNI Unlike ‘basic science research, which has as its goal the generation of fundamental knowledge concerning biological or behavioural processes, nursing research 1s driven by the need to promote excellence mm nursing science as a guide for nursing practice Although a few nurse scientists have conducted PNI research to date, additional studies are needed to generate new knowledge concerning mund-body interactions in health and illness and to develop stratogies that promote mental and physical well-being in persons at risk for ymmune dysfunction This paper highlights the few recently conducted nursing studies grounded in a PNI framework to illustrate the utsity of PNIan advancing nursing science status Unlike baste science research, which has a ts goal INTRODUCTION the generation of fundamental knowledge concerning bio- ‘Nursing research involves scientific mquury into the bro- logical or behavioural processes, nursing research s driven Topeal and behavioural responses of individuals to actual by the need to promote excellence in nursing scence as & or potential boalth problems, as well asthe study of nurs- guide for nursing practice ing therapeutics undertaken to waluenco changes n health Evolving. from the smitiel conception of Florence Nightingale and through the more recent development of dunce Pjur} ¥ Ze Department of tomarcing/ _-ursungtheones, the disrphne of nursing bas mavntasned epee Pes M Zr pe eg abc focus of canng, Thus, nurses have both tt Congress ara. Chega ns 0612, USA rvely and theoretically considered the unity of biological (© 1996 Blackwell Scienco Lid 657IM Zeller ot al and behavioural processes when providing patient care Recent advances m basic science research have confirmed the close interactions betwoon behavioural and biological processes on the orgamismic, cellular and molecular levels Despite these advances, there remains a dearth of com- prehensive research-based knowledge to explicate the relationshups of behavioural factors to certain illnesses and to guide the use of biobehavioural approaches in health promotion, disease prevention and symptom management Recently, « group of leading nurse researchers have pro- moted the idea that nursing science and behavioural research should become more tightly mterwoven with bio- logical research (Cowan et al 1993) The growing field of psychoneuroxmmunology (PNI) provides a framework for nurse researchers to use in examining relationships between behavioural and biological phenomena and their aniluences on health outcomes Nis concerned with the mechantsms of bidirectional neuroendocrine-immune system anteraction (Rabin et af 1989) According to this framework, depression, pain or stressful situations can influence ammune system mntegnty via neuroendocrine pathways Conversely, 1mmune- denved products can induce neurochemical and physio- logical changes 1n the central nervous system (CNS) PNI hhas been used by investigators in various disciplines to guide the examination of possible relationshups between behavioural factors and the progression of 1mmunolog- tcally mediated diseases, such as human 1mmunodefici- fency virus (HIV) anfecton (Solomon 1987) Others have ‘uthzed this framework to evaluate the role of immune products inthe development of CNS disturbances (Grulian ef al 1990) Most recently, behavioural scientists have used @ PNI focus to study the influence of therapies such as relaxation and imagery on ummune functon (Halley 1991, Kiecolt-Glaser & Glaser 1992, Pelletier 1992) ‘Nursing research programmes grounded in PNI will be able to contnbute to the generation of new knowledge con- ‘cerning mind-body interactions in health and illness and to the development of strategies that promote mental and. physical well-being in persons at risk of ummune dysfunc- tion This paper highlights the few recently conducted ‘nursing studies grounded in a PNT framework m order to allustrate the utility of PNI in advancing nursing science HISTORICAL DEVELOPMENT OF PSYCHONEUROIMMUNOLOGY For centunes it had been observed that illness often fol- lowed stressful life events (Locke 1982} However, 1t was not until 1964, when Goorge Solomon proposed @ new ce called ‘psychounmunology’, that systematic attempts were made to identify relationships among stres- sors, ummunological dysfunction and disease (Solomon & ‘Moos 1964) Greeted with imal scepticism, interest in this new science exploded in the mid-1970s when it was demonstrated that immunological responses could be classically conditioned (Ader & Cohen 1975) Because this finding implicated neuroendocrine pathways m the relationship between stressors and ammunological responses, the science was renamed ‘psychoneurommmun- ology’ Today, scientists and clinicians generally agree that PNI research can elucidate the normal and pathological processes underlying human adaptation, leading to chni- cally significant interventions for mamntaning health and treating illness (Ader 1992) MECHANISMS OF NEUROENDOCRI! IMMUNE SYSTEM INTERACTIONS PNI investigators have identified numerous mechanisms through which the CNS and immune system anteract, smeluding darect anatomical linkages and soluble neuroen- docrine derived products In response to psychobiological stimuls such as pain or stress, a number of these mechan- 1sms may be activated, including those depicted somewhat sumphstcally in Figure1 As allustrated at Path A, neurological fibres (especially sympathetic fibres of the Peychobiologcal ‘mut Beta-endorph aT acTH Figure 1_PNIinteracton pathways (© 1006 Blackwell Science Ltd, fournal of Advanced Nursing, 23, 657-664PNTand nursing research ‘autonomic nervous system) have been shown to directly innervate immune system tissues These anatomical hink- ‘ngs may influence immunological integnty, functioning ‘via spocific recoptors for neurotransmitters (eg cat- echolamines, opioid peptides and dopamine) on the sur face of immune cells Achvation of the sympathetic: adrenomedullary system (Path B) results 1n the release of soluble products such as catecholammes and encephalins, ‘both of which are known to have complex unmunomodul- atory effects Sumulation of the hypothalamc-pituitary-adreno- cortical system (Path C) leads to the elaboration of cortico- tropin (ACTH), endorphins and glucocorticoids Some of these hormones have been reported to have immtuno- potentiating effects, whereas others are prmanly ammuno- suppressive Immune-denved products, with structural and biological properties identical to neuroendocrne hormones, may also be elaborated im response to certain psychobiological stimuli (Path D) Factors such as interleukin-1 (IL-1), ACTH, and beta-endorphin (among others) have the potential to influence the behaviour of the neuroendocrine system (For comprehensive PNI reviews, see Ader ef al 1991, Newberry et al 1991, Plotmkoff et al 1991) IMMUNOMODULATORY EFFECTS OF STRESSORS Although a number of psychobiological stmult have been reported to influence immune system funchoning, stress hhas been studied most extensively in this regard Recent PNI research has provided considerable evidence that psychological stress and 1lIness are related through immu- ‘nomodulation, although the underlying mechanisms are only partially understood (reviewed n Rabin et al 1989, Hhllhouse et al 1991, Newberry et al 1991, Herbert & Coben 1993, Stein & Miller 1993) In general, stress down regulates the immune system, with perhaps the most important link betwoen stress and sllness snvolving the offects of elevated levels of cortisol Cortisol 1s primarily ammunosuppressive, with reductions 1n leucocyte num bers and function (pnmanly T-lymphocyte and monocyte subsets) and natural kller (NK) cell actaty (Rabin et al 1989, O'Leary 1990, Hallhouse et al 1991) Reduced pro- duction of cytokmes mn response to cortisol interferes with uartually all components of the immune system (Munck & Guyre 1991) Several resoarchers have investigated whether psycho- logical stressors are associated with the onset of illness 1m humans or a less favourable clinical course mn persons already ill (for reviews, see Cohen & Williamson 1991, Newborry ef al 1991, Vogel & Bower 1991) In a recent study st was found that self-reported psychological stress ‘was associated with the onset of clinical colds in persons exposed to respiratory viruses The relationship wat {© 1006 Blackwell Science Ltd, journal of Advanced Nursing, 28. 657-664 dose-dependent, that 18, the rate of colds mcreasod as subjects’ stress levels increased (Cohen et al 1991) Other anvestigators have demonstrated that latent viruses (6g Epstein-Barr, herpes simplex) can be reactivated by stres- sors such as mantal seperation (Kiecolt-Glaser. Fisher et al 1987), carmg for an indrvidual with Alzheumer’s disease (Kiecolt-Glaser, Glaser et a! 1987), or taking ‘medical school examinations (Glaser et al 1987) In HIV- infected gay men, depression has been reported to be associated with immunological parameters which are pre- Aictive of disease progression (Burack et al 1993, Kemeny et al 1994), although this finding has not been consistent (Lyketsos et al 1993) The rletionshp between stress and the development of, cancer has received considerable attention In mouse ‘models, thas been shown that stressors can anfluence both susceptibility to and growth of virally induced tumours (Ruley 1975, Sklar & Anisman 1980} In humans, the relationships among stressors and cancer have been less clear For example, relationships have been found between stressors and susceptibility to breast cancer (Levy et al 1987) and rate of breast cancer recurrence (Ramirez et al 1989), yet other investigators have found no relationship between stressors and the incidence of cancer (Prestman et al 1985, Zonderman et al 1989) or survival of cancor patients (Cassileth ef al 1985) Several investgators have suggested that negative affect, or psychological distress, may be a common denominator m demonstrated relation- ships between stressors and diseases such as cancer (Predman & Booth-Kewley 1987, Smith 1993) Confhcting research results may relate to findings that certain charactenstcs of stressors, such as their chromicty, intensity, predictabihty and controllabihty, determne their influences on the immuno system (Shavit 1991, Simith 1993) The disparate findings in the nterature also may relate to methodological differences among the stud- 1es, a8 well as to individual patterns of response to differ- ent stressors Much more research 1s needed to discern the complex interactions through which stress can modulate :mmune system functioning and thereby influence health ‘and well-being ‘Although inital PNItesearch was focused on identifying ‘mechanisms underlying neuroendocrne-immune system imteractions, in recent years researchers have begun to emphasize the application of psychoneuroummunologic knowledge to clinical populations (Ader 1992) A number ofbiobehavioural strategies, including relaxation, imagery, biofeedback and hypnosis, have been used to modulate ‘mmune function and have generally boon associated with positive immunological changes (Halley 1991, Kiocolt- Glaser & Glaser 1992) Psychosocial interventions to pro- rote ummunocompetence have been tested inthe elderly (Kiecolt-Glaser et al 1985), those with cancer (Fawzy et al +1890a, 1990b). and persons with HIV infection (Antont et al 1991, Esterling etal 1992)