Friday, September 27, 2002

This presentation is part of : Womens Health Studies: Responses and Risks

Natural Killer Cell Function in Midlife Women with and without Fibromyalgia

Carol A. Landis, RN, DNSc, professor1, Martha J. Lentz, RN, PhD, research associate professor1, Joyce Tsuji, BA, research technologist1, Dedra Buchwald, MD, professor2, and Joan Shaver, RN, PhD, FAAN, professor and dean3. (1) Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA, (2) Medicine, University of Washington, Seattle, WA, USA, (3) College of Nursing, University of Illinois at Chicago, Chicago, IL, USA

Objective: Fibromyalgia (FM) is a complex syndrome characterized by chronic pain, poor sleep, fatigue and psychological distress. The pathophysiology of this disorder is thought to involve functional changes in the central nervous system that lead to central sensitization associated with diffuse pain, arousal patterns during sleep, and altered neuroendocrine activity. In our schema, these central changes lead to peripheral changes, potentially compromising host defenses. Natural killer (NK) cells are an important defense against viral-infected and tumor cells. In this study we compared percentages of NK cells, percentages of activated NK (IL-2 receptor cell surface expression) and T (CD 69 activation antigen) cells, and NK cell activity (cytotoxicity) in women with and without FM. We hypothesized that NK cell function would be suppressed in women with FM because lower percentages and reduced NK activity have been shown in individuals with pain, with poor sleep, and a related illness, chronic fatigue syndrome.

Design: The study design was descriptive/comparative.

Population, Sample, Setting, Years: A convenience sample of 32 midlife women with and 34 women without FM were studied. Women with a diagnosis of FM based on published criteria and pain (greater than or equal to 4 on a 10 point scale) were recruited from an academic referral clinic devoted to the study of fatigue. Sedentary women without pain (less than or equal to 3 on a 10 point scale) were recruited from the community. The setting was a biobehavioral research laboratory in a school of nursing. The participants were studied between 1996 and 2000.

Concept or Variables Studied Together or Intervention and Outcome Variable(s): Indicators of host defenses (immune function) were compared between midlife women with FM and pain (mean, 45.3 ± 8.3 years) and midlife women without pain (mean, 42.8 ± 7.4 years). Clinical characteristics that might influence immune activity (e.g., age, height and weight to derive body mass index, depression, psychological distress) were also measured.

Methods: Age and height and weight were obtained during the initial telephone screen and later verified when the participants came to the laboratory. Blood samples for immune assays were obtained the morning after the second or baseline night the participants spent in the sleep laboratory. Mononuclear cells were separated from whole blood by Ficoll-Hypaque gradient centrifugation and frozen. Cryopreserved cells were thawed, percent viability determined and 2-color flow cytometry was used to quantify the percentage of NK cells and activated NK and T cells. NK cell activity was measured by a 4-hour standard chromium release assay and lytic units at 20% killing were calculated. A short version of the Beck depression inventory assessed depressive symptoms and the global score (GSI) of the SCL-90 measured psychological distress. Student's t-test or Mann-Whitney U test were used to evaluate group differences.

Findings: There were no significant differences in age and body mass index (kg/m2) between women with FM (27.6 ± 5.7) and control women (25.4 ± 4.1). As expected women with FM had higher depression (7.5 ± 5.2) and psychological distress (0.8 ± 0.5) scores compared to control women (depression: 1.1 ± 1.4; psychological distress: 0.1 ± 0.1; both p < .001). The percentage of NK cells was lower in women with FM (7.8 ± 3.3) compared to control women (10.6 ± 4.9), but the percentage of NK cells that expressed the IL-2 receptor as a marker of NK cell activation was higher in women with FM (3.9 ± 3.1) compared to control women (2.5 ± 1.5). There were no differences in the percentage of T cells with CD69 expressed on the cell surface as indication of cell activation. NK cell activity expressed as lytic units at 20% killing effectiveness was lower in women with FM (5.6 ± 6.0) compared to control women (8.5 ± 8.7), but these differences were not statistically significant given the large variability between groups.

Conclusion: Despite the presence of a chronic condition with indication of mild depression and psychological distress, women with FM in this sample showed minimal differences in immune indicators of NK cell function compared with women of similar age and body size.

Implications: Additional analyses to compare relationships among the variables in this study may provide insights into the impact of central nervous system changes in FM on immune parameters and the potential for compromised host defenses. However, health care providers are cautioned not to make assumptions that individuals with chronic illnesses characterized by pain necessarily have compromised immune functioning.

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