Abstract
BackgroundThe variation of immune cell activities over time is an immanent property of the human immune system, as can be measured by the stimulated secretion of cytokines in cell cultures. However, inter-individual variability is considerably higher. Especially the latter is the major reason why it has not been possible to establish international standard values for cytokines as was possible for other parameters, such as leukocyte sub-population numbers. In this trial, a highly standardized whole-blood culture model (TrueCulture®), developed to characterise drug effects on cells of the human immune system in clinical trials, was used to analyse cytokine patterns in the blood samples of 12 healthy subjects over a period of one month.MethodsAfter an overnight fast, 12 healthy subjects donated blood three times a week on three consecutive days over a period of 4 weeks. TruCulture® blood collection and whole-blood culture systems were used to measure whole-blood leukocyte stimulation. The levels of IL-2, IL-5, IL-13, IL-6, IL-8, IL-10, IFNγ, and MCP-1 in the culture supernatants were quantified by sandwich ELISA.ResultsThe pattern of cytokine concentrations in the supernatants of the stimulated whole-blood cultures was highly individual, but considerably stable over the whole observation period of 4 weeks.ConclusionsBy using TruCulture® it seems feasible to determine subject-specific cytokine reference patterns, for example under healthy conditions, or before starting an experimental treatment, e.g. during a clinical trial, against which changes in the behaviour of the immune system can be detected more accurately in future.
Highlights
The variation of immune cell activities over time is an immanent property of the human immune system, as can be measured by the stimulated secretion of cytokines in cell cultures
The immune cells of each blood donor were challenged with a standardised stimulus in whole-blood cultures, which had been developed for the peculiar situation of clinical trials (TruCultureW)
With regards to the mediator levels measured in these whole-blood culture supernatants, virtually each of the cytokines and chemokines showed a more or less subject-specific and relatively stable average concentration level throughout the whole observation period
Summary
The variation of immune cell activities over time is an immanent property of the human immune system, as can be measured by the stimulated secretion of cytokines in cell cultures. Leukocytes respond to various types of signals, such as infectious agents [1], tumour cells [2], dying cells [3], allergens [4], stress hormones [5], and changes in the composition of the intestinal microbiota [6], and – last, but not least – drug activities [7] This diversity of daily challenges makes it hard to find a truly resting immune system in humans at all. Each subject represents a highly complex genetic combination of polymorphisms [8], making its immune system a virtually unique selection of high and low responder states Together, this necessarily leads to enormous interindividual variability regarding cytokine levels in plasma, serum, or culture supernatants, thereby preventing the defining of internationally accepted standard values for cytokines, chemokines, or other mediators related to immune cell activation. This makes it highly problematic to compare results from different groups and different trials [10]
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