Elizabeth J. Corwin

Understanding Cytokines Part I: Physiology and Mechanism of Action

This is the first of a 2-part article on understanding cytokines. Cytokines are intercellular signaling proteins released from virtually all nucleated cells that influence growth and cellular proliferation in a wide range of tissues. Cytokines have immune modulating effects and are understood to control most of the physical and psychological symptoms associated with infection and inflammation. Cytokines also influence reproduction and bone remodeling. Dysregulation of the cytokine cellular system has significant implications in the development of a variety of illnesses, including most autoimmune disorders, many diseases of the cardiovascular system, osteoporosis, asthma, and depression. For nurses to be adequately informed when caring for clients with chronic illnesses and to be sufficiently knowledgeable when evaluating client outcomes, an understanding of the physiology of cytokines, the occurrences of dysregulation, and the role of cytokines in health and illness is essential. In Part I of this review, cytokine physiology is presented, with an emphasis on characteristics, categories, and mechanism of action. Specific instances of cytokine function in health and disease and implications for nursing research and practice are presented in Part II.

Symptoms of Postpartum Depression Associated With Elevated Levels of Interleukin-1 Beta During the First Month Postpartum

Postpartum depression (PPD) is a devastating disorder that may carry lifetime consequences. Although several psychosocial risks for PPD have been identified, biological contributors are unclear. Elevated inflammatory cytokines contribute to depression in nonpregnant, nonpostpartum populations; yet, their role in PPD has been minimally studied. The objective of this study is to determine whether inflammatory cytokines early in the postpartum period contribute to the development of PPD. Women were recruited within 24 hr of delivery, and 26 provided urine for analysis of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) on postpartum days 7, 14, and 28. Participants completed a depression symptom survey (Centers for Epidemiologic Studies Depression Scale; CES-D) on Day 28. An increase in IL-1β was seen on Day 14 in women with symptoms of depression (CES-D ! 11) on Day 28 compared to levels in women without depressive symptoms (F = 4.50, p = .045). These preliminary findings suggest elevated IL-1β early in the postpartum period may increase the risk of PPD. Further studies involving a larger sample of women, including those clinically diagnosed with PPD, are required.

Predictors of Fatigue in Healthy Young Adults: Moderating Effects of Cigarette Smoking and Gender

Fatigue is a common complaint of patients seen in primary care. Factors that contribute to fatigue in a patient population include poor health status, psychological stress, poor nutrition, and pregnancy. Less well understood are factors that contribute to fatigue among healthy, nonpregnant individuals. Within the framework of the theory of unpleasant symptoms, 40 healthy young smoking and nonsmoking adults between the ages of 18 and 35 were evaluated to determine self-report level of fatigue and contributing physiological, psychological, and situational factors. Results indicate that while self-report of fatigue did not vary in this population based on gender, subjects who were moderate to heavy cigarette smokers were significantly more fatigued than were nonsmokers (F= 10.24, df = 1, 38, P < 0.01), with the effect being specific to male smokers. Self-report of fatigue did not correlate with body mass index, baseline inflammatory or immune status, or blood pressure. Positive psychological and situational predictors of fatigue included depression (r = 0.556, P < 0.001), state anxiety (r = 0.569, P < 0.001), sleep quality (r = –0.399, P < 0.05), and sleep quantity (r = –0.411, P < 0.05). These results suggest that psychological and situational factors are key contributors to fatigue in young adults and that smoking is a risk factor for fatigue in men.

Interleukin-1ß elevation during the postpartum period

During the postpartum period, women frequently report increased fatigue, which, if severe, may interfere with maternal-child bonding, delay a new mother’s return to her activities of daily living, and contribute to depression. Several studies have sought to determine psychosocial contributions to fatigue during the postpartum period, but few evaluate any physiological changes that may contribute to fatigue during this time. The following study was designed to test whether the potent, proinflammatory cytokine interleukin-1beta (IL-1ß), known to be a physiological mediator of fatigue in several clinical and experimental conditions, is elevated in women during the postpartum period and whether it might be related to symptoms of fatigue. Levels of fatigue and the urinary excretion of IL-1ß were measured in 26 women over 4 weeks postpartum. Correlations between fatigue and activation of the inflammatory response were investigated. Results demonstrated a significant elevation in IL-1ß during the postpartum period compared to control participants (p < .05) and a significant, although delayed, correlation between IL-1ß elevation and fatigue (p < .05). These results suggest that activation of the inflammatory response, as reflected by elevation in urinary IL-1ß, occurs in association with postpartum fatigue. Studies to explore further this association and to identify specific mechanisms of action are needed.

What is the Slowest-Yet-Normal Cervical Dilation Rate Among Nulliparous Women With Spontaneous Labor Onset?

OBJECTIVEnTo integrate research literature that has provided insights into the cervical dilation rate that may best describe the slowest-yet-normal dilation rate among nulliparous women when beginning with criteria commonly associated with active labor onset.nnnDATA SOURCESnA literature search from 1950 through 2008 was conducted using the Medline electronic database, reference lists from identified articles, and other key references.nnnSTUDY SELECTIONnResearch reports written in English with a focus on the cervical dilation and/or labor duration of low-risk, nulliparous women with spontaneous labor onset.nnnDATA EXTRACTIONnClassic and contemporary research literature was reviewed and organized under the following subheadings: Friedman Studies, Partograph Studies, Active Management of Labor Studies, Additional Studies.nnnDATA SYNTHESISnAn integrative review of the literature approximated the slowest-yet-normal cervical dilation rate for nulliparous women when beginning with criteria commonly associated with active labor.nnnCONCLUSIONSnThe slowest-yet-normal linear dilation rate approximates 0.5 cm/hour for low-risk, nulliparous women with spontaneous labor onset when starting at dilatations traditionally associated with active labor onset. However, this linear rate must be evaluated judiciously in light of the physiological acceleration of dilation that occurs during typical labor. Given this, cervical dilation for this population is likely slower than 0.5 cm/hour in earlier active labor and faster in more advanced active labor. Faster dilation expectations (e.g., 1 cm/hour) likely contribute to an overdiagnosis of dystocia (slow, abnormal progression of labor) in contemporary practice and, subsequently, to an overuse of interventions aimed at accelerating labor progress.

Proposed biological linkages between obesity, stress, and inefficient uterine contractility during labor in humans

Cesarean delivery has reached epidemic proportions in contemporary western healthcare. For otherwise healthy first-time (nulliparous) women at term gestation with a single fetus in a head down position, the most common clinical diagnosis prompting cesarean delivery is dystocia, including clinical terms such as uterine dysfunction, failure to progress, arrest of dilation and/or arrest of descent of the fetal head. In 2006, the cesarean rate for this lowest risk population of childbearing women was 26% in the United States despite the goal of Healthy People 2010 to reduce this rate to 15% from a baseline of 18% in 1998. While multiple lines of evidence suggest that the nulliparous uterus is particularly vulnerable to a diagnosis of uterine dysfunction during labor, pathophysiologic explanations for this dysfunction have not been well described. The acute stress response has been implicated as one factor in this dysfunction for many years, while more recently the growing epidemic of adiposity among women of childbearing age has been suggested as an additional pathway by which myometrial cell function may be disrupted. Using both clinical and in vitro evidence, we hypothesize a combined model in which pathways of acute stress and changes associated with maternal adiposity, particularly exaggerated levels of cholesterol and leptin, may independently and synergistically impair the contractile apparatus of the myocyte leading to the clinical diagnosis of uterine dystocia and subsequent cesarean delivery.

Postpartum fatigue and evidence-based interventions.

The aim of this article is to review postpartum fatigue, especially as it relates to the occurrence and pathophysiology of three common postpartum conditions known to contribute to fatigue: anemia, infection/inflammation, and thyroid dysfunction. Fatigue is an unrelenting condition that affects physical and mental health, and it has implications for everyday activities, motivation, and social interactions. Although individuals of all ages and both genders are at risk for developing fatigue, postpartum fatigue is particularly challenging, because the new mother has demanding life tasks to accomplish during this period of time. Postpartum fatigue may impact postpartum maternal role attainment and may place a woman at increased risk for postpartum depression. Although several treatable physiological conditions common during the postpartum period are known to increase fatigue, none of these conditions is a part of the usual assessment of healthy postpartum women. For many women, subtle fatigue may develop, linger or worsen, and even lead to depression, with both the woman and her care provider unaware.

The Heritability of Postpartum Depression

Postpartum depression (PPD) is a serious mood disorder that may carry life-long consequences for a woman and her family. Multiple risk factors for PPD have been identified, including psychosocial, situational, and biological stimuli, several of which are experienced by most, if not all, postpartum women. Given the commonality of these risk factors, it is unclear why fewer than 20% of postpartum women actually develop PPD. In this review, we suggest that different susceptibility to PPD among postpartum women may be explained by the presence or absence of genetic variants that confer increased risk. We review three categories of genes known to code for proteins associated with depression in the general population or proteins known to be affected by childbirth for their possible association with PPD, including genes related to central nervous system monoamine availability, proinflammatory cytokines, and brain neuropeptides. Only two studies are available in the literature to date specifically looking at polymorphisms in postpartum women as related to PPD; both are concerned with monoamine availability. These are discussed in further depth. Conclusions regarding the contribution of genetic polymorphisms to the development of PPD are mixed. Ultimately, the complexity of the disorder and the interrelationships among different genes thought to contribute to depression suggest that much more research is required to understand the heritability of PPD. The complexity of the disorder also suggests that epigenetic influences must be considered as well when discussing susceptibility.

The Impact of Educational Message Framing on Adherence to Continuous Positive Airway Pressure Therapy

Although of proven health benefit to persons with obstructive sleep apnea (OSA), adherence to continuous positive airway pressure (CPAP) therapy is suboptimal, with patterns of use that are established early and that are not easily altered after the initial experience. In a randomized controlled trial, 70 participants with OSA and cardiovascular disease were assigned to receive either positively or negatively framed education about CPAP. Objective adherence was measured following 30 days of home CPAP therapy. Daytime sleepiness, dispositional optimism, self-efficacy, and depression were also evaluated at baseline and after 30 days. CPAP use was greater in the group receiving negative message framing (p = .015).

The concept of epigenetics and its role in the development of cardiovascular disease: commentary on "new and emerging theories of cardiovascular disease".

The article published in this volume of Biological Research for Nursing by Alpert (Alpert 2004 [this issue]) reviews the hypotheses that infectious disease and/or an elevation in serum iron play a role in the etiology of cardiovascular (CV) disease. The article points out that although some research is suggestive for each factor contributing to CV disease, findings from clinical studies fail to demonstrate that either factor is causative. In this commentary, it is proposed that the complex nature of CV disease and the difficulty in identifying a single causal agent for its development may be partially explained by considering one of the most intriguing and actively studied concepts of our time: epigenetics. Understanding epigenetics may lead those holding a holistic view of health and disease to include in their perspectives the influence of the prenatal or even preconceptual environment on health outcomes and to reevaluate assumptions regarding the relationship between genotype and phenotype.