Trauma often leads to complications like organ failure and inflammation, significantly contributing to mortality. Alcohol plays a major role in post-traumatic outcomes and is linked to a high number of hospital admissions. Alcohol is known to disrupt immune responses, causing both immune suppression and inflammation. This dual effect suggests alcohol has a complex, "double-edged" impact on the immune system, but the underlying mechanisms after trauma remain unclear.

NF-κB is a key regulator of inflammation, and alcohol can either activate or suppress its activity. Deubiquitinating enzymes (DUBs), such as A20, control NF-κB signaling by modifying key proteins. A20 helps balance pro- and anti-inflammatory signals, but how alcohol affects DUBs in trauma is not well understood. Additionally, other “signaling” molecules such as e.g. extracellular vesicles (EVs) may play a role in transmitting inflammatory signals after trauma, further complicating the inflammatory response.

This project aims to explore how DUBs regulate NF-κB activity after trauma and alcohol exposure, and to investigate the role of alcohol in modulating NF-κB signaling in liver and lung. We also study the influence of alcohol-intoxicated trauma patient sera on inflammation and examine how e.g. extracellular vesicles contribute to the transmission of inflammation post-trauma. In vivo studies with DUB knock-out mice support to clarify if and how DUBs influence inflammation and associated organ damage after trauma.

Identifying patients at risk for severe complications, particularly those with alcohol use, is crucial for improving treatment outcomes. This research could provide insights into how alcohol modulates immune responses and the role of extracellular vesicles in transmitting inflammation, offering potential therapeutic targets to reduce post-traumatic complications and enhance patient care.

Publikationen:

1. Wang T, Alalman O, Wagner A, Bülow JM, Rinderknecht H, Relja B. A20 modulates ethanol-induced suppression of NF-κB-mediated hepatic inflammation in in vitro polytrauma conditions. Shock. 2025. Suppl. Issue Sept.
2. Becker N, Bülow JM, Wagner A, Eguchi A, Rinderknecht H, Relja B. Early sepsis risk assessment in multiple trauma patients using the sepsis as trauma outcome prediction (stop) score – a prognostic accuracy of 59.4% within 24 hours post-emergency department admission. Shock. 2025. Suppl. Issue Sept.
3. Bülow JM, Vo MT, Wagner A, Rinderknecht H, Relja B. Alcohol-dependent regulation of energy metabolism by NF-κB signaling in HepG2 cells. Shock. 2025. Suppl. Issue Sept.
4. Herminghaus A, Totskyi M, Vollmer C, Dimski T, Brandenburger T, Kuebart A, Rinderknecht H, Bergmann CB, Vernikouskaya I, Bülow JM, Becker N, Relja B. Diagnostic utility of IL-18 plasma levels in distinguishing abdominal from non-abdominal sepsis. Front Immunol. 2025 May 29;16:1591262. doi: 10.3389/fimmu.2025.1591262. PMID: 40510342
5. SturmR, Haag F, RinderknechtH, BülowJM, Wagner N , ZabelJ, Bergmann CB, Marzi I, Relja B. Granulocyte function in response to acute alcohol consumption: temporal shifts from proinflammatory activation to antiinflammatory modulation in healthy volunteers. J Leukoc Biol. 2025 Jun 4;117(6):qiaf081. doi: 10.1093/jleuko/qiaf081. PMID: 40479504
6. Bülow JM, Rinderknecht H, Becker N, Köhler K, Wagner A, Yang Y, Bundkirchen K, Neunaber C, Relja B. Exploring the Bone-Liver Axis: Impact of Acute Ethanol Intoxication on Post-Traumatic Liver Inflammation and Damage Following Femur Fracture. Int J Mol Sci. 2025 May 21;26(10):4923. doi: 10.3390/ijms26104923. PMID: 40430063
7. Becker N, Bülow JM, Franz N, Marzi I, Gebhard F, Eguchi A, Rinderknecht H, Relja B. Assessment of early indicators for sepsis development in multiple trauma patients - the Sepsis as Trauma Outcome Prediction (STOP) score. Shock. 2025 May 14;64(2):187–197. doi: 10.1097/SHK.0000000000002626. PMID: 40367515
8. Reichardt LM, Hindelang B, Süberkrüb L, Hamberger KL, Graw JA, Schuetze K, Zechendorf E, Mannes M, Halbgebauer R, Wohlgemuth L, Gebhard F, Huber-Lang M, Relja B, Bergmann CB. Absolute lymphocyte count trajectory predicts clinical outcome in severely injured patients. Eur J Trauma Emerg Surg. 2025 May 2;51(1):190. doi: 10.1007/s00068-025-02864-0. PMID: 40314767
9. Jooss T, Maier K, Reichardt LM, Hindelang B, Süberkrüb L, Hamberger KL, Bülow JM, Schuetze K, Gebhard F, Mannes M, Halbgebauer R, Wohlgemuth L, Huber-Lang M, Relja B, Bergmann CB. Dynamic functional assessment of T cells reveals an early suppression correlating with adverse outcome in polytraumatized patients. Front Immunol. 2025 Mar 24;16:1538516. doi: 10.3389/fimmu.2025.1538516. PMID: 40196124

10. Sturm R, Haag F, Bergmann CB, Marzi I, Relja B. Alcohol drinking leads to sex-dependent differentiation of T cells. Eur J Trauma Emerg Surg. 2025 Jan 27;51(1):87. doi: 10.1007/s00068-024-02732-3. PMID: 39870931

11. Becker N, Franz N, Eguchi A, Wagner A, Sturm R, Rinderknecht H, Kobayashi Y, Iwasa M, Weber B, Marzi I, Relja B. Elevated extracellular particle concentration in plasma predicts in-hospital mortality after severe trauma. Front Immunol. 2024 Jun 12;15:1390380. doi: 10.3389/fimmu.2024.1390380. eCollection 2024. PMID: 38933277

12. Fachet M, Mushunuri RV, Bergmann CB, Marzi I, Hoeschen C, Relja B. Utilizing predictive machine-learning modelling unveils feature-based risk assessment system for hyperinflammatory patterns and infectious outcomes in polytrauma. Front Immunol. 2023 Dec 12;14:1281674. doi: 10.3389/fimmu.2023.1281674. eCollection 2023. PMID: 38193076

13. Hörauf JA, Singh A, Voth M, Moheimani H, Schindler CR, Relja B, Leppik L, Marzi I, Henrich D. Limited Diagnostic Value of miRNAs in Early Trauma-Induced Liver Injury: Only miRNA-122 Emerges as a Late-Phase Marker. Diagnostics (Basel). 2025 Jan 14;15(2):179. doi: 10.3390/diagnostics15020179. PMID: 39857063

14. Weber B, Ritter A, Han J, Schaible I, Sturm R, Relja B, Huber-Lang M, Hildebrand F, Pallas C, Widera M, Henrich D, Marzi I, Leppik L. Development of a Sampling and Storage Protocol of Extracellular Vesicles (EVs)-Establishment of the First EV Biobank for Polytraumatized Patients. Int J Mol Sci. 2024 May 22;25(11):5645. doi: 10.3390/ijms25115645. PMID: 38891833