Many cytokines exhibit wide biological variation (1) and there may be circadian and seasonal variation (6). Cytokine levels are influenced by biological variables such as age, gender and body mass index, and environmental factors such as diet, microbiome and genetic factors (7).
Cytokine concentrations may increase substantially during illness. A number of different conditions such as sepsis, rejection reactions following transplantation, cardiovascular disease, cancer, rheumatic disorders, overweight, Alzheimer's disease, asthma, kidney damage, Parkinson's disease, depression (1) and diabetes with chronic periodontitis may result in increased cytokine levels (8).
There are still many challenges associated with the diagnostic and prognostic use of cytokines, including a number of analytical methods that are not standardised or directly comparable, and a lack of internationally established reference ranges for the various technologies. We recently published an article investigating optimal sampling conditions (9). It is especially important that whole blood is not left to stand before centrifuging, because it is the blood cells that produce and release cytokines after sampling. We recommend EDTA plasma as sampling material for measuring these cytokines. In the study, we calculated reference intervals for the 27 cytokines in EDTA plasma from 162 healthy individuals, analysed by means of multiplex immunoassay (9). In healthy individuals, many cytokines were either unmeasurable or detectable only in very low concentrations (1, 9).