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Elevated Serum Soluble CD163 Indicates Macrophage Activation: A Potential Biomarker for Inflammation in Complex
Nadia Kriek1, Krishna Bharwani1, Maaike Dirckx1
1Center for Pain Medicine, Department of Anesthesiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Background:
Several studies point towards the involvement of the immune system (especially the monocyte-macrophage system) in the pathophysiology of Complex Regional Pain Syndrome (CRPS), as shown by increased levels of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. These cytokines are primarily released from pro-inflammatory M1 macrophages, but are difficult to measure in a clinical setting. Investigating the activity of tissue-resident macrophages by measuring soluble CD163 (sCD163) in serum is much more clinically applicable. sCD163 could potentially be a biomarker for determining inflammation in CRPS and would have direct consequences for the choice of therapy. The aim of this study is to investigate the tissue-resident macrophage activation in CRPS with sCD163 and explore the relationship between soluble IL-2R, which is a marker for T-cell activation, and sCD163.
Methods:
The sCD163 levels were determined in this retrospective cohort study (MEC-2020-0716) in serum of CRPS patients (n = 22) and healthy controls (n = 27). ELISA kits were used to measure the levels of these markers. Data on demographics, pain scores (11-point Numeric Rating Scale: NRS), sIL-2R levels, signs and symptoms, and CRPS disease severity were also recorded.
Results:
The median serum sCD163 level was significantly higher in CRPS patients (CRPS 960.5 pg/mL [Q3-Q1: 1211.5-623.9] than in healthy controls 677.0 pg/mL [Q3-Q1: 828.0-469.5], p = 0.008). There was a statistically significant positive correlation between sCD163 and sIL-2R in the CRPS group (rs = 0.577; p = 0.005), but not in the healthy control group (rs = 0.359; p = 0.066).
Conclusion:
Our findings indicate that pro-inflammatory activation of tissue-resident macrophages and thus the monocyte-macrophage system is part of CRPS pathogenesis. The monocyte-macrophage system is an interesting new target for future research into the pathogenesis of CRPS, but also has potential for diagnosis, particularly for assessing the involvement of the immune system and choice of therapy in the individual CRPS patient. Measurement of the sCD163 could be a potential biomarker for inflammation in CRPS.
Trial Registration:
This retrospective cohort study was approved by the Medical Ethics Committee of the Erasmus MC University Medical Center (MEC-2020-0716).
