Abstract
BackgroundInflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers.MethodsBased on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis.ResultsHsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3’-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83).ConclusionsComprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.
Highlights
Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic
In addition to a general feeling of illness, there are a number of different inflammatory parameters that are of clinical importance, including highsensitivity C-reactive protein, white blood cell count (WBC), and fibrinogen
Chronic inflammation is considered integral to the development of serious systemic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, gastrointestinal disorders, and rheumatoid arthritis
Summary
Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In addition to localized inflammatory reactions at the site of injury (redness, swelling, overheating, pain and disturbed function of the affected tissue or organ), reactions of the entire organism can be affected, depending on the severity of inflammation [1]. Both the local and systemic responses initiated by an inflammatory process indicate an imbalance in metabolism in the tissues affected. In addition to a general feeling of illness, there are a number of different inflammatory parameters that are of clinical importance, including highsensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen. Chronic inflammation is considered integral to the development of serious systemic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, gastrointestinal disorders, and rheumatoid arthritis
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