The Diagnostic Discriminative Power of Serum IL-6 Levels for Chlamydia Trachomatis Infection

Abstract

Background: Chlamydia trachomatis represents one of the most prevalent sexually transmitted infections, frequently persisting without noticeable symptoms, yet capable of leading to adverse outcomes such as infertility. The identification of reliable biomarkers has been emphasized as essential for enhancing early detection strategies.

Objective: This research was conducted to evaluate the potential utility of circulating interleukin-6 (IL-6) as a biomarker for the diagnosis of Chlamydia trachomatis infection.

Methods: A case–control approach was adopted, comprising 52 individuals with laboratory-confirmed C. trachomatis infection and 48 apparently healthy participants serving as controls. Serum IL-6 levels were quantified using the enzyme-linked immunosorbent assay (ELISA). Group differences were examined through independent samples t-tests, while variations associated with different infection sites were assessed using analysis of variance (ANOVA). Additionally, the diagnostic performance of IL-6 was evaluated via receiver operating characteristic (ROC) curve analysis to determine its accuracy in distinguishing infected from non-infected subjects.

Results: Patients had significantly elevated IL-6 levels (18.6 ± 5.2 pg/ml) compared to controls (12.4 ± 4.1 pg/ml, p < 0.03). Analysis of serum IL-6 levels across different anatomical infection sites indicated that concentrations were highest in urogenital infections (19.2 ± 5.1 pg/ml), whereas rectal infections exhibited moderately lower values (17.5 ± 4.6 pg/ml). The area under the curve (AUC) was 0.84, with an optimal diagnostic threshold determined at 15.5 pg/ml, yielding a sensitivity of 80.8% and specificity of 77.1%. These findings suggest that IL-6 levels are markedly elevated in individuals affected by Chlamydia trachomatis, supporting its potential role as a reliable biomarker, particularly for urogenital infection sites.

Keywords:

Interleukin-6, Chlamydia trachomatis, AUC, Sensitivity, Specificity

References

Balcioglu, Y. H., Koseoglu, H., & Goktas, M. T. (2018). Diagnostic value of serum interleukin-6 and procalcitonin in patients with sepsis. Journal of Infection and Chemotherapy, 24(2), 101–106.

Budai, A., Kovacs, K., & Balazs, K. (2019). Cytokine responses in chronic bacterial infections: The role of IL-6. Cytokine, 120, 23–30.

Chen, G., Wu, D., Guo, W., Cao, Y., Huang, D., Wang, H., & Zhang, X. (2020). Clinical and immunological features of IL-6 in severe pneumonia. Journal of Clinical Investigation, 130(5), 2620–2629.

Dalrymple, S. A., Slattery, R., Aud, D. M., Krishna, M., Lucian, L. A., & Murray, R. (1996). Interleukin‐6 is required for a protective immune response to systemic Escherichia coli infection. Infection and Immunity, 64(8), 3231-3235.

de Man, P., van Kooten, C., Aarden, L., Engberg, I., Linder, H., & Svanborg Edén, C. (1989). Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection. Infection and Immunity, 57(11), 3383-3388.

Geisler, W. M., Morrison, S. G., & Hook, E. W. (2017). Cytokine responses in cervical epithelial cells infected with Chlamydia trachomatis. Infection and Immunity, 85(3), e00914–16.

Gitsels, A., Sanders, N., & Vanrompay, D. (2019). Chlamydial infection models: From in vitro to in vivo. Pathogens and Disease, 77(2), ftz009.

Al-Fahham, A. A., Zwamel, A. H., Mousa, H. M., & Abdul Azeez, B. A. M. (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.

Li, H., Wang, Y., & Zhang, X. (2021). Combined biomarkers for the diagnosis of bacterial infections: Role of IL-6. Frontiers in Immunology, 12, 657–663.

Liu, H., Xu, M., & Wang, H. (2019). Serum IL-6 and IL-8 as diagnostic biomarkers in sexually transmitted infections. International Journal of STD & AIDS, 30(10), 987–994.

Masson, L., Passmore, J. A., Liebenberg, L. J., Werner, L., Baxter, C., Arnold, K. B., & Karim, Q. A. (2016). Genital inflammation and the risk of HIV acquisition in women. Clinical Infectious Diseases, 61(2), 260–269.

Morrison, R. P., Belland, R. J., & Byrne, G. I. (2020). Host inflammatory responses to Chlamydia trachomatis infections. Microbes and Infection, 22(6–7), 239–246.

Mpiga, P., Scidmore, M. A., & Stephens, R. S. (2006). Sustained interleukin-6 and interleukin-8 expression following infection with Chlamydia trachomatis serovar L2 in a HeLa/THP-1 cell co-culture model. Scandinavian Journal of Immunology, 64(5), 460-470.

O’Connell, C. M., & Balaji, A. (2020). Chlamydia-host interactions: Role of IL-6 in pathogenesis. Frontiers in Cellular and Infection Microbiology, 10, 286.

Russell, D., Johnston, C. D., Fairlie, D. P., & Timms, P. (2014). The IL-6 response to Chlamydia trachomatis from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection. BMC Immunology, 14(1), 23.

Sun, X., Tian, Q., Wang, L., Xue, M., & Zhong, G. (2017). IL-6-mediated signaling pathways limit Chlamydia muridarum infection and exacerbate its pathogenicity in the mouse genital tract. Microbes and Infection, 19(11), 536-545.

Tanaka, T., Narazaki, M., & Kishimoto, T. (2016). Immunotherapeutic implications of IL-6 blockade in inflammatory diseases. Nature Reviews Rheumatology, 12(1), 48–62.

Vodstrcil, L. A., Plummer, E. L., & Fairley, C. K. (2017). The role of STIs and inflammatory cytokines in tubal factor infertility. Human Reproduction Update, 23(6), 693–705.

World Health Organization. (2023, July 17). Chlamydia [Fact sheet]. https://www.who.int/news-room/fact-sheets/detail/chlamydia.