Work

Caffeine and paracetamol co-purify with C-reactive protein from surgical patients

Year: 2026

Type: article

Abstract: Background Cell damage caused by surgical trauma leads to the release of intracellular adenosine triphosphate (ATP), which activates purinergic P2X7 receptors and induces the maturation and secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β). Excessive IL-1β production following major abdominal surgery can drive uncontrolled inflammation and increase the risk of postoperative complications and organ dysfunction. Our previous work demonstrated that binding of phosphocholine (PC) to pentameric C-reactive protein (pCRP) mediates an anti-inflammatory function by suppressing ATP-induced IL-1β release through activation of nicotinic acetylcholine receptors. The present study aimed to investigate the anti-inflammatory potential of circulating CRP in surgical patients and to identify endogenous compounds associated with CRP that could interact with its established PC-binding pocket. Methods Pre- and postoperative blood samples were collected from patients undergoing major abdominal surgery. Whole blood cells, peripheral blood mononuclear cells, and monocytic THP-1 cells were primed with lipopolysaccharide and subsequently stimulated with ATP in the presence or absence of autologous plasma or CRP-depleted plasma. Compounds co-purifying with circulating CRP were identified by immunoprecipitation followed by liquid chromatography and mass spectrometry (LC/MS). Complementary molecular docking analyses were performed to predict the potential binding of the identified compounds to the established PC-binding pocket of CRP. Results Patient plasma inhibited ATP-induced IL-1β release in a dose-dependent manner. However, depletion of CRP did not significantly alter the inhibitory effect of postoperative plasma. Immunoprecipitation followed by LC/MS identified caffeine and paracetamol as the predominant compounds co-purifying with circulating CRP. Complementary molecular docking predicted that both compounds could occupy the established PC-binding pocket of CRP. Conclusions Together, the LC/MS and computational findings link caffeine and paracetamol to the previously described PC-dependent immunomodulatory functions of CRP and suggest that small molecules other than PC may influence CRP biology. These observations raise the possibility that commonly used perioperative medications modulate CRP-dependent immune functions, with potential implications for postoperative immune regulation. Further studies are warranted to establish the relationship between caffeine, paracetamol, and CRP.

Source: European journal of medical research

DOI: 10.1186/s40001-026-05025-0