The Diagnostic Power Of IL-6 In the Diagnosis of Acute Cholecystitis

Abstract

Background: Cholecystitis is an inflammatory condition of the gallbladder that varies in severity and is associated with elevated inflammatory markers such as interleukin-6 (IL-6). Understanding the relationship between IL-6 levels and disease severity may improve diagnosis and management.

Methods:
This case–control study enrolled 68 patients aged 22 to 45 years diagnosed with cholecystitis at Nasiriyah Teaching Hospital, Thi‑Qar City, Iraq, from March 2024 to February 2025. Patients were classified into mild, moderate, and severe groups based on clinical and imaging criteria. Forty healthy patients without gallbladder disease served as controls. Exclusion criteria included recent antimicrobial treatment, chronic illnesses, pregnancy, and lactation. Serum IL-6 levels were measured by ELISA following standardized protocols.

Results:
Mean serum IL-6 concentration was significantly higher in patients (85.2 ± 21.4 pg/ml) compared to controls (32.7 ± 12.6 pg/ml) (p < 0.001). IL-6 levels progressively increased with cholecystitis severity: mild (64.3 ± 12.8 pg/ml), moderate (83.7 ± 14.5 pg/ml), and severe (106.5 ± 18.2 pg/ml), with statistically significant differences among groups (ANOVA, F = 18.46, p < 0.001). Post hoc analysis confirmed that each severity group differed significantly in IL-6 levels. Receiver operating characteristic (ROC) curve analysis showed excellent diagnostic accuracy for IL-6 with an area under the curve of 0.914. At a cut-off value of 58.0 pg/ml, IL-6 achieved a sensitivity of 89.6% and specificity of 82.4% for distinguishing cholecystitis patients from healthy controls (p < 0.001).

Conclusions:
Serum IL-6 is markedly elevated in patients with cholecystitis and correlates strongly with disease severity. IL-6 demonstrates high diagnostic accuracy and may serve as a valuable biomarker for identifying and stratifying cholecystitis in clinical settings.

Keywords:

Interleukin-6, Cholecystitis, Sensitivity, Specificity

References

Akyurek, N., Salman, B., Irkörücü, O., Yuksel, O., Sare, M., & Tatlicioglu, E. (2005). The role of interleukin-6 as an early marker in the diagnosis of acute abdominal diseases. Journal of Investigative Surgery, 18(6), 345–351. https://doi.org/10.1080/08941930500337641

Al-Fahham, A.A. (2018) Development of New LSD Formula when Unequal Observations Numbers of Observations Are. Open Journal of Statistics, , 8, 258-263.https://doi.org/10.4236/ojs.2018.82016.

Al‑Shamlan, N. A., Al‑Obaid, S., Al‑Sultan, M., Al‑Mutairi, R., & Al‑Daihani, M. (2022). Role of IL-6 in diagnosing and predicting complications of cholecystitis. BMC Gastroenterology, 22, 140. https://doi.org/10.1186/s12876-022-02186-8

Baharoon, S., Al‑Hameed, F., Al‑Omari, A., Al‑Qurashi, A., & Al‑Kattan, K. (2023). Diagnostic accuracy of ultrasound for acute cholecystitis: A systematic review. Frontiers in Surgery, 10, 1147205. https://doi.org/10.3389/fsurg.2023.1147205

El‑Molla, A. M., Abdel‑Aziz, H. M., Mahmoud, A. M., & Salem, A. A. (2023). Serum interleukin‑6 as a marker of severity in acute cholecystitis. International Journal of Surgery Open, 49, 100581. https://doi.org/10.1016/j.ijso.2023.100581

Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine, 340(6), 448–454. https://doi.org/10.1056/NEJM199902113400607

Khan, M. A., Ali, S., Hussain, M., & Ahmed, S. (2022). Diagnostic value of serum IL-6 in patients with acute cholecystitis. Journal of Clinical and Diagnostic Research, 16(6), OC16–OC20. https://doi.org/10.7860/JCDR/2022/56271.16393

Kim, S. J., Park, J. Y., Lee, Y. J., Kim, J. H., & Kang, C. M. (2022). Combined IL‑6 and CRP measurement for diagnosis of complicated cholecystitis. Journal of Hepato‑Biliary‑Pancreatic Sciences, 29(2), 156–164. https://doi.org/10.1002/jhbp.1032

Liu, Y., Zhang, X., Chen, H., & Wang, Z. (2023). IL‑6 in the diagnosis of acute abdominal inflammation. BMC Emergency Medicine, 23, 12. https://doi.org/10.1186/s12873-023-00760-x

Pereira, J., et al. (2020). Acute cholecystitis: diagnosis and treatment. Current Surgery Reports, 8(3), 12.

Salman, R. S., Abdul Azeez, B. A. M., Munshid, M. C., & Al-fahham, A. A. (2024). Inflammatory response and pathophysiology of IL-6 overproduction: A review article. International Journal of Health & Medical Research, 3(8), 568–572. https://doi.org/10.58806/ijhmr.2024.v3i08n05

Suzuki, K., Takada, T., Kawarada, Y., & Nimura, Y. (2021). Cytokine dynamics in acute cholecystitis. Surgery Today, 51(3), 327–334. https://doi.org/10.1007/s00595-020-02147-9

Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295. https://doi.org/10.1101/cshperspect.a016295

Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL‑6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295. https://doi.org/10.1101/cshperspect.a016295

Yacoub, W. N., Petrosyan, M., & Phelan, M. J. (2021). Evidence-based approach to the acute abdomen. Surgical Clinics of North America, 101(1), 1–16.

Yokoe, M., Hata, J., Takada, T., Strasberg, S. M., & Tokyo Guidelines Revision Committee. (2018). Tokyo Guidelines 2018: Diagnostic criteria and severity grading of acute cholecystitis. Journal of Hepato‑Biliary‑Pancreatic Sciences, 25(1), 41–54. https://doi.org/10.1002/jhbp.515