Bidirectional Cause–Effect Relationship Between Urinary Interleukin-6 and Mood, Irritation, and Mental Activity in a Breast Cancer Survivor

Abstract

This “integrative single-case study” investigated the bidirectional cause and effect relations between various emotional states (i.e., mood, irritation, mental activity) and urinary IL-6 levels in a 49-year-old female breast cancer survivor (woman) under conditions of “life as it is lived.” During a period of 28 days, the patient collected her entire urine in 12-h intervals for IL-6 measurement and completed each morning and evening a list of adjectives regarding mood, irritation, and mental activity (55 measurements in total). Autoregressive integrated moving average modeling revealed a 4-day (circasemiseptan) cycle in the IL-6 time series. Furthermore, cross-correlational analyses after controlling for serial dependencies (significance level: p < 0.05) showed that worsening in mood and increases in irritation were followed by increases in urinary IL-6 levels with temporal delays between 12 and 36 h. In the opposite direction of effect, increases in urinary IL-6 levels were followed by elevations in mood and mental activity as well as decreases in irritation with temporal delays between 48 and 72 h. These results from cross-correlational analyses suggest that IL-6 may have a regulatory function in psychoneuroimmunological interplay and that, under certain conditions, IL-6 may be involved in health rather than sickness behavior. Moreover, the findings of this study are indicators of real-life negative feedback loops and are in line with psychoneuroimmunological research postulating complex brain-to-body-to-brain network-like structures.

Case Report: Dynamic Interdependencies Between Complementary and Alternative Medicine (CAM) Practice, Urinary Interleukin-6 Levels, and Fatigue in a Breast Cancer Survivor

“…Third, in this patient, IL-6 was followed by increases in positive emotional states and decreases in negative emotional states (22) and, as the current investigation demonstrated, decreases rather than increases in fatigue. Thus, in contrast to established thinking (8,9), our data from this patient show that IL-6 was involved in health behavior rather than sickness behavior (22).…”

“…This integrative single-case study is part of a larger project on breast cancer survivors that examines the effects of emotionally meaningful incidents on stress system activity. Various results dealing with this patient have already been published (22,23,35,36).…”

“…Further details of the study design are described in Schubert et al ( 22 , 23 ), Haberkorn et al ( 35 ), and Singer et al ( 36 ).…”

“…Aspirin on an irregular basis was the only medication the patient took. Further details are given in Schubert et al ( 22 , 23 ), Haberkorn et al ( 35 ), and Singer et al ( 36 ).…”

“…The heterogeneous findings to date on the relationship between CAM practice and inflammatory markers and between CAM practice and CaRF may be due in part to methodological issues inherent in conventional biomedical research approaches (e.g., inadequate statistical power, diversity of cancer disease characteristics and treatment regimens, biased and heterogeneous composition of subjects, diverse biomarker examination materials, diversity with regard to CAM program frequency and duration, failure to consider the possibility of therapist effect, and usage of various forms of comparative control/placebo) ( 7 , 18 , 21 ). On a more basic level, we propose that the inconsistent findings are also attributable to the inadequacy of conventional research methods (e.g., pre-post design, standardized questionnaires) in grasping (a) the dynamic complexity of highly fluctuating (circulating) biomarkers such as IL-6 and (b) the complex psychosocial factors involved in the application of CAM use (e.g., personal meaning) ( 22 – 26 ).…”