Serum Concentrations of Interleukin-6 Are Increased When Sampled Through an Indwelling Venous Catheter

Abstract

Circadian and ultradian variation is a prominent feature of most endogenous biodynamic processes and has been extensively studied in neuroendocrine systems (1). Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in many age-related diseases, including postmenopausal osteoporosis (2)(3). Estrogen has been shown to directly inhibit IL-6 production (4)(5). Very little information on the circadian rhythms and no information on ultradian rhythms of IL-6 or other pro-inflammatory cytokines exists. Recent research has demonstrated a strong reciprocal interaction between IL-6 and the hypothalamic–pituitary–adrenal (HPA) axis (6)(7). Specifically, recombinant IL-6 has been shown to stimulate the HPA axis in humans (8). The recent availability of highly sensitive assays for measuring IL-6 provides the opportunity to study the rhythmic pattern of this cytokine. A study in men, in which samples were collected every 3 h by direct venipuncture, showed a large circadian variation in circulating IL-6 with a peak at 0100 and a nadir at 1000 (9). More frequent sampling is required to elucidate ultradian fluctuations, which typically have periods of 60 to 90 min (10). For practical reasons, indwelling venous catheters rather than direct venipunctures have been used for studying frequently sampled time series. We designed a study, using an indwelling venous catheter for continuous integrated 15-min sample collection, to establish the normal variations of circulating IL-6 over 24 h in healthy postmenopausal women, and to assess the effect of estrogen replacement therapy on these patterns. In studying the first subject, it became apparent that serum IL-6 reached higher values than expected. Here, we demonstrate that an indwelling peripheral venous catheter leads to local tissue production of IL-6. We also demonstrate that this local production of IL-6 does not affect endogenous cortisol concentrations. The study protocol was approved by the University of Wisconsin …