Fu J, Zhang YY. Correlation between inflammatory markers and disease severity in ulcerative colitis. World J Gastrointest Surg 2025; 17(12): 108880 [DOI: 10.4240/wjgs.v17.i12.108880]
Corresponding Author of This Article
Jie Fu, MD, College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, No. 188 Tanhualin, Wuhan 430065, Hubei Province, China. fujie266@126.com
Research Domain of This Article
Gastroenterology & Hepatology
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Retrospective Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 27, 2025 (publication date) through Dec 25, 2025
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World Journal of Gastrointestinal Surgery
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1948-9366
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Fu J, Zhang YY. Correlation between inflammatory markers and disease severity in ulcerative colitis. World J Gastrointest Surg 2025; 17(12): 108880 [DOI: 10.4240/wjgs.v17.i12.108880]
Jie Fu, College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
Yue-Yu Zhang, Department of Rehabilitation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Yue-Yu Zhang, College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
Author contributions: Fu J was responsible for writing, data analysis, and visualization; Zhang YY took charge of conceptualization; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by the 2019 TCM Evidence-based Practice Capacity Building Project of the State Administration of Traditional Chinese Medicine, No. 2019XZZX-ZJ006; and the 2020 “Special Project on Traditional Chinese Medicine Ancient Books and Characteristic Technology Inheritance”, No. 295.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Central Hospital of Wuhan.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jie Fu, MD, College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, No. 188 Tanhualin, Wuhan 430065, Hubei Province, China. fujie266@126.com
Received: July 11, 2025 Revised: August 18, 2025 Accepted: October 21, 2025 Published online: December 27, 2025 Processing time: 166 Days and 17.2 Hours
Abstract
BACKGROUND
Although histopathological examination via colonoscopy is the benchmark for ulcerative colitis (UC) diagnosis, its limitations underscore the urgency of identifying noninvasive diagnostic markers.
AIM
To investigate the clinical relevance of systemic inflammatory markers in assessing disease severity among patients with UC.
METHODS
In this study, 117 consecutive patients with UC hospitalized between January 2024 and January 2025 were analyzed and stratified by disease severity using the modified Mayo score: Mild (n = 37), moderate (n = 45), and severe (n = 35) groups. Demographic and clinical data were recorded, and serum concentrations of inflammatory markers-interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) - were measured and compared across the groups. Correlation analyses (Spearman’s rank) were conducted to evaluate the relationships between cytokine levels and disease severity. Disease severity-associated predictors were identified through regression (univariate and multivariate) analyses, supplemented by sensitivity testing to validate consistency. The diagnostic performance of inflammatory markers for disease progression was assessed using the receiver operating characteristic curve.
RESULTS
Serum IL-6, TNF-α, and CRP levels exhibited a significant stepwise increase with worsening UC severity. Each inflammatory marker demonstrated a strong positive correlation with disease severity. Multivariate analysis identified smoking history, alcohol abuse, IL-6, TNF-α, and CRP as independent predictors of disease progression. In the sensitivity testing, directional effects of these variables were aligned (all odds ratios > 1), indicating robust results. Receiver operating characteristic analysis indicated that the combined cytokine panel demonstrated superior diagnostic accuracy (area under the curve 0.917, 88.6% sensitivity, 80.5% specificity) when compared with individual markers (area under the curves, 0.763-0.820).
CONCLUSION
IL-6, TNF-α, and CRP levels strongly correlate with the progression of UC and may serve as reliable biomarkers for disease activity. The combined measurement of these markers could facilitate the early identification of high-risk patients, enabling prompt delivery of clinical intervention and personalized management.
Core Tip: The study evaluated whether interleukin-6, tumor necrosis factor-α, and C-reactive protein levels correlate with the severity of ulcerative colitis (UC). Analyses confirm strong positive relationships, supporting their utility as noninvasive biomarkers for UC progression. Of note, the interleukin-6 + tumor necrosis factor-α + C-reactive protein combination outperformed single-marker testing in identifying severe UC cases.
Citation: Fu J, Zhang YY. Correlation between inflammatory markers and disease severity in ulcerative colitis. World J Gastrointest Surg 2025; 17(12): 108880
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by persistent mucosal inflammation predominantly affecting the colon and rectum. The pathogenesis is characterized by the complex interaction of immune dysregulation, compromised intestinal barrier function, and environmental factors[1,2]. Recognized risk factors include smoking history, familial predisposition to IBD, and certain genetic polymorphisms, which collectively contribute to susceptibility to diseases[3]. UC has become a global health concern with increasing incidence rates, and epidemiological data indicate that approximately 1 million individuals each are affected in the United States and Europe, imposing a substantial socioeconomic burden[4]. Clinically, active UC manifests with debilitating symptoms such as fatigue, abdominal pain, arthralgia, fecal incontinence, and bloody diarrhea, severely compromising the psychosocial well-being, quality of life, and social functioning of patients[5]. The disease follows a relapsing–remitting course, and inadequate disease control predisposes patients to recurrent symptoms, progressive intestinal damage, and high colorectal cancer risk[6]. Consequently, achieving sustained remission and preventing relapse represent critical therapeutic objectives, requiring accurate assessment of disease severity for risk stratification and therapeutic decision-making[7]. The current gold-standard evaluation relies on colonoscopy alongside histopathological examination, an invasive approach associated with patient discomfort and procedural risks such as perforation[8,9]. This condition underscores the urgent need for reliable noninvasive biomarkers.
Emerging data highlight the pivotal role of interleukin (IL)-6 in intestinal homeostasis, where it modulates epithelial barrier integrity, orchestrates intestinal immune responses, and mediates host–microbial interactions at the mucosal interface, rendering it a potential therapeutic target in UC[10]. Both IL-6 and tumor necrosis factor (TNF)-α are canonical proinflammatory cytokines, with significantly increased levels in patients with UC[11]. Notably, TNF-α overactivity contributes to mucosal barrier dysfunction, whereas anti-TNF-α biologics have demonstrated efficacy in promoting mucosal healing[12]. Additionally, C-reactive protein (CRP), an acute-phase reactant downstream of IL-6 signaling, correlates with the disease activity of UC[13]. This study posits that serum IL-6, TNF-α, and CRP levels significantly correlated with UC severity and may serve as clinically useful noninvasive biomarkers for disease monitoring. Given the paucity of robust evidence in this domain, this study aimed to provide substantive evidence supporting their utility in clinical practice.
MATERIALS AND METHODS
Case selection
Inclusion criteria: (1) Fulfillment of the diagnostic criteria for UC[14]; (2) Age ≥ 18 years; (3) Complete serum cytokine 12-item testing during hospitalization; (4) First-time diagnosis and treatment; (5) Presence of clinical manifestations, such as abdominal pain, diarrhea, bloody stools, recurrent episodes, and hyperactive bowel sounds; and (6) Availability of complete medical records.
Exclusion criteria: (1) History of colon-related surgery; (2) Use of corticosteroids, immunosuppressants, antibiotics, or other relevant medications within 1 month before admission; (3) Concurrent infections (e.g., pulmonary, urinary tract, or bloodstream infections); (4) Pregnancy or lactation; (5) Hepatic/renal dysfunction or coagulation disorders; and (6) Critical illness precluding tolerance of colonoscopy or other diagnostic procedures.
Following rigorous screening based on the above criteria, 117 patients with UC admitted to our hospital between January 2024 and January 2025 were enrolled in this study. They were grouped following the disease severity stratification using the modified Mayo score[15]: Mild (3-5 points, mild group), moderate (score points, 6-10, moderate group), and severe (11-12 points, severe group) activity.
Methods
Clinical data were collected from all the enrolled patients. Fasting venous blood samples (4 mL) were obtained from each participant on the morning of their second hospitalization day. Following standardized centrifugation protocols, serum was isolated and aliquoted for analysis. Serum concentrations of key inflammatory biomarkers, such as IL-6, TNF-α, and CRP, were quantitatively determined using commercially available enzyme-linked immunosorbent assay kits according to manufacturer protocols.
Data collection and outcome measures
Demographic and clinical data, including age, sex, body mass index, smoking status, and history of alcohol consumption, were systematically compared across disease severity subgroups (mild, moderate, and severe UC). Comparative analyses of serum inflammatory marker levels (IL-6, TNF-α, and CRP) were conducted among the severity groups. Spearman correlation analyses were conducted to evaluate potential associations of serum inflammatory marker levels with the severity of UC. Univariate analysis and binary logistic regression modeling were employed to screen potential clinical factors influencing the severity of UC. The predictive capacity of serum IL-6, TNF-α, and CRP levels was analyzed using the receiver operating characteristic (ROC) curve to assess disease severity in patients with UC.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). Normally distributed continuous variables were presented as mean ± SD and compared using Student’s t-test. Categorical variables were expressed as frequencies (percentages) and analyzed using the χ2 test. The associations between serum IL-6, TNF-α, and CRP levels and disease severity were assessed using Spearman’s rank correlation analysis. Univariate analysis followed by binary logistic regression modeling was performed to identify potential risk factors that influence disease severity in patients with UC. To assess sensitivity, 1000 bootstrap resamples were applied to significant predictors in the multivariate model, generating odds ratio (OR) distribution graphs. The predictive performance of each biomarker was further evaluated by the ROC curve. A two-tailed P value < 0.05 was considered significant.
RESULTS
Baseline characteristics of patients with UC
A cohort of 117 patients with UC was stratified by disease severity using the modified Mayo score: Mild (n = 37, 31.6%), moderate (n = 45, 38.5%), and severe (n = 35, 29.9%). Demographic and clinical characteristics were well-balanced across the groups (all P > 0.05), ensuring comparability for subsequent analyses (Table 1).
Table 1 Baseline demographic and clinical characteristics of ulcerative colitis patients, n (%).
Levels of inflammatory markers progressively increased with worsening disease severity. Serum levels of IL-6, TNF-α, and CRP demonstrated significant stepwise increases across mild, moderate, and severe UC groups (all P < 0.01) (Figure 1).
Figure 1 Association between ulcerative colitis severity and systemic inflammatory markers.aP < 0.01; bP < 0.001. A: Interleukin-6 concentrations across severity groups; B: Tumor necrosis factor-alpha concentrations across severity groups; C: C-reactive protein concentrations across severity groups. IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CRP: C-reactive protein.
Correlation analysis of inflammation and disease severity
Spearman rank correlation analysis confirmed strong positive correlations between disease severity and serum levels of IL-6, TNF-α, and CRP (all P < 0.01) (Figure 2).
Figure 2 Correlation matrices of inflammatory markers with ulcerative colitis severity.
A: Interleukin-6 vs Mayo score; B: Tumor necrosis factor-alpha vs Mayo score; C: C-reactive protein vs Mayo score. IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CRP: C-reactive protein.
Determinants of disease severity in patients with UC
This study evaluated 117 patients with UC stratified by disease severity: 82 with mild-to-moderate presentation vs 35 with severe manifestations. Preliminary univariate screening revealed several clinical and biochemical factors that showed correlation, such as smoking history, alcohol abuse, IL-6, TNF-α, and CRP levels (all P < 0.05). Subsequent multivariate binary logistic regression modeling incorporating these variables revealed several independent predictors of disease severity: Smoking history (OR = 4.185), alcohol abuse (OR = 3.565), IL-6 (OR = 2.826), TNF-α (OR = 3.396), and CRP (OR = 2.849) (all P < 0.05). Additionally, each examined variable showed a unidirectional effect (OR > 1) in the sensitivity analysis, supporting the robustness of the results (Tables 2 and 3, Figure 3).
Figure 3 Odds ratio distributions from Bootstrap sensitivity testing (n = 1000 iterations).
A: Odds ratio (OR) distribution for smoking history sensitivity analysis; B: Alcohol abuse history OR distribution analysis; C: Interleukin-6-related OR stability across resamples; D: Tumor necrosis factor-alpha-associated OR consistency analysis; E: C-reactive protein-based OR robustness evaluation. OR: Odds ratio; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CRP: C-reactive protein.
Table 2 Univariate analysis of factors associated with disease severity in ulcerative colitis patients, n (%).
Predictive performance of the multifactor combined model
ROC curve analysis was conducted to compare the diagnostic efficacy between single-biomarker and multifactor predictive models for the severity of UC. The results demonstrated that IL-6 alone exhibited an area under the curve (AUC) of 0.797, with a sensitivity of 62.86% and specificity of 95.12% at an optimal cutoff value of 18.94 pg/mL. TNF-α alone showed an AUC of 0.820, achieving 65.71% sensitivity and 85.37% specificity at a cutoff of 24.85 pg/mL. CRP alone yielded an AUC of 0.763, with 74.29% sensitivity and 71.95% specificity at a cutoff of 14.32 mg/L. Notably, the combined model integrating all three biomarkers demonstrated a significantly improved predictive performance, achieving an AUC of 0.917, with 88.57% sensitivity and 80.49% specificity at a cutoff probability of 0.26. For detailed results, refer to Figure 4 (ROC curves) and Table 4 (predictive performance metrics).
UC is a chronic IBD characterized by complex cytokine dysregulation and persistent intestinal inflammation, particularly in moderate-to-severe cases[16]. To improve disease management strategies and clinical monitoring of disease progression, the association between serum biomarkers (IL-6, TNF-α, and CRP) and UC severity was systematically evaluated, and their predictive value for disease progression was assessed.
The present findings demonstrated a significant dose-dependent increase in IL-6, TNF-α, and CRP levels with worsening UC, indicating their potential involvement in disease pathogenesis and clinical deterioration. The levels of both IL-6 and TNF-α, which are pivotal in the pathogenesis and treatment of various acute and chronic diseases, were markedly high in our patient cohorts, corroborating previous reports of their overexpression in the intestinal tissues of patients with UC[17,18]. These observations further substantiate the mechanistic contributions of the IL-6-driven T-helper cell 17 pathway and TNF-α-mediated nuclear factor κB signaling cascade in the pathogenesis of UC[19,20]. Additionally, the increase in CRP, as a hepatic acute-phase reactant, was proportional to the systemic inflammatory burden, thereby serving as a sensitive and clinically useful surrogate marker for assessing disease severity in acute severe UC[21].
Furthermore, correlation analyses revealed significant positive associations among all three biomarkers (particularly TNF-α and CRP) and disease severity of UC, proposing their potential utility as reliable indicators for monitoring disease progression. Wine et al[22] demonstrated that IL-6 correlated with disease activity in severe UC in pediatrics and may help predict therapeutic response to intravenous corticosteroid therapy. Previous studies have established that high mucosal TNF-α levels predict treatment responsiveness in Crohn’s disease (a related IBD subtype), supporting its role in guiding early therapeutic decisions[23]. Rivière et al[24] identified CRP as a valid noninvasive marker for deep ulceration in UC, which facilitates optimized treatment selection in acute severe cases. Moreover, Huang et al[25] proposed that a composite index that combines CRP and bilirubin could predict disease activity in UC, aiding in the assessment of clinical remission and endoscopic mucosal healing. Numerous studies have investigated the relationship between serum biomarkers and UC severity. Hong et al[26] reported a strong correlation between serum L-arginine levels and UC severity; however, its clinical applicability may be limited because of the competitive inhibition by L-ornithine and L-lysine. Manoria et al[27] observed that serum IL-23 levels increase with disease severity and are closely associated with immune dysregulation, highlighting its potential as a therapeutic target to modulate disease progression. Similarly, Marinelli et al[28] demonstrated that high serum proprotein convertase subtilisin/kexin type 9 levels exhibit a significant positive correlation with both UC disease activity and potential cardiovascular risk biomarkers, suggesting its dual role as a prognostic indicator.
In this study, the initial univariate analysis identified smoking history, alcohol abuse, IL-6, TNF-α, and CRP as key factors associated with the severity of UC. Subsequent multivariate analysis confirmed these as independent predictors, highlighting the potential clinical utility of combining lifestyle modifications with targeted therapies in the management of UC. Mechanistically, nicotine disrupts the composition of the gut microbiota, enhances toll-like receptor 4-mediated IL-6 and TNF-α overproduction, and impairs mucosal healing by suppressing vascular endothelial growth factor signaling, thereby exacerbating tissue damage. Similarly, alcohol exerts detrimental effects through acetaldehyde-induced intestinal epithelial barrier dysfunction, microbial dysbiosis, and amplified responses of proinflammatory cytokine (IL-6 and TNF-α), collectively accelerating UC progression[29-32]. Notably, Kondo et al[33] reported that heavy smokers who quit before age 40 and heavy drinkers who ceased alcohol consumption at or after age 40 face a high UC risk. Nevertheless, research on factors contributing to UC exacerbation remains limited. Finally, ROC curve analysis yielded AUC values of 0.797 (IL-6), 0.820 (TNF-α), and 0.763 (CRP) for predicting disease severity, with IL-6 showing the highest specificity (95.12%). Importantly, the combination of all three biomarkers achieved superior diagnostic performance (AUC = 0.917), maintaining high sensitivity (88.57%) and specificity (80.49%).
The limitations of this study must be addressed. First, the results of the analysis of single-center-derived data (n = 117), despite meeting basic analytical requirements, could reflect geographic bias. Expanding to multicenter prospective trials would strengthen the validity of the results. Second, current data cannot confirm whether treatment (hormonal agents/biologics)-induced biomarker changes (e.g., post-therapy declines) could predict clinical outcomes because longitudinal monitoring data were unavailable. Third, expanded analyses of inflammatory marker dynamics during therapy must be conducted to establish their prognostic utility. Fourth, the link between biomarkers and UC-related complications such as intestinal perforation and colorectal neoplasia remains unexamined. Investigating this aspect would strengthen prognostic evaluations. Lastly, a cost-effectiveness comparison between combined vs single serum inflammatory marker testing in UC was not conducted. Adding such data would support translational applications.
CONCLUSION
This study demonstrates a significant positive correlation between IL-6, TNF-α, and CRP levels and disease severity in patients with UC. These biomarkers can serve as reliable serum indicators for evaluating the progression of UC. Importantly, their combined use (AUC = 0.917) exhibits superior diagnostic accuracy over individual markers, facilitating earlier identification of severe UC cases and supporting timely clinical intervention with intensive therapy.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade C
Creativity or Innovation: Grade B
Scientific Significance: Grade C
P-Reviewer: Bak TS, PhD, Denmark S-Editor: Bai Y L-Editor: A P-Editor: Xu ZH
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