# Seminal Interleukin-6 as a Biomarker of Inflammation, Oxidative Stress, and Sperm Dysfunction in Infertile Men

**Authors:** Loïc Koumba, Mariame Kabbour, Salma Ed-doumy, Mariem Norredine, Ahlam Zarhouti, Modou Mamoune Mbaye, Bouchra Ghazi, Noureddine Louanjli, Moncef Benkhalifa, Rajaa Ait Mhand, Ouafaa Aniq Filali

PMC · DOI: 10.3390/diseases14020049 · Diseases · 2026-01-30

## TL;DR

This study shows that high levels of IL-6 in semen are linked to poor sperm quality and inflammation in infertile men, suggesting it could be a useful biomarker.

## Contribution

The study identifies seminal IL-6 as a novel biomarker for inflammation, oxidative stress, and sperm dysfunction in male infertility.

## Key findings

- Higher seminal IL-6 levels correlate with reduced sperm motility, vitality, and increased DNA fragmentation.
- IL-6 independently predicts elevated leukocyte counts and bacteriospermia in infertile men.
- Seminal IL-6 is detectable in all samples and shows strong associations with oxidative stress markers.

## Abstract

Background/Objectives: Interleukin-6 (IL-6), a pleiotropic cytokine involved in immune regulation, is consistently detected in human semen, even in the absence of overt infection. Its contribution to sperm dysfunction, oxidative stress, and inflammation remains incompletely understood. This study evaluated the associations between seminal IL-6 concentrations and markers of semen quality, oxidative stress, nuclear integrity, and genital tract inflammation in infertile men. Methods: A cohort of 204 infertile men was assessed. Seminal IL-6 was quantified by electrochemiluminescence immunoassay. Semen parameters, malondialdehyde (MDA), catalase (CAT) activity, sperm DNA fragmentation index (DFI), sperm chromatin decondensation index (SDI), leukocytospermia, and bacteriospermia were measured. Analyses included correlation testing, IL-6 threshold stratification (<30, 30–60, 60–100, ≥100 pg/mL), and multivariate regression. Results: IL-6 was detectable in all samples (median: 31.52 pg/mL; range: 1.5–5000 pg/mL). Higher IL-6 levels were significantly associated with reduced sperm concentration, progressive motility, and vitality, and with increased DFI, SDI, MDA, leukocyte counts, and bacteriospermia (p < 0.001). In multivariate models, IL-6 independently predicted reduced progressive motility (β = −0.005; p = 0.032) and elevated leukocyte count (β = 0.0018; p < 0.0001). Logistic regression further showed that IL-6 increased the odds of DFI ≥ 30%, SDI ≥ 30%, and bacteriospermia (p < 0.05). Conclusions: Seminal IL-6 emerges as a sensitive biomarker of immuno-oxidative stress and sperm dysfunction in infertile men. Its integration into clinical evaluation may improve the assessment of inflammatory and oxidative contributors to male infertility.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Chemicals:** malondialdehyde (PubChem CID 10964)

## Full-text entities

- **Genes:** CAT (catalase) [NCBI Gene 847], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283] {aka 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1}, CYP11A1 (cytochrome P450 family 11 subfamily A member 1) [NCBI Gene 1583] {aka CYP11A, CYPXIA1, P450SCC}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, STAR (steroidogenic acute regulatory protein) [NCBI Gene 6770] {aka STARD1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** infected (MESH:D007239), dysbiosis (MESH:D064806), febrile episode (MESH:C580065), injury to (MESH:D014947), reduced progressive motility (MESH:D015835), Inflammation (MESH:D007249), seminal (MESH:C565993), semen abnormalities (MESH:C000711649), azoospermia (MESH:D053713), mitochondrial dysregulation (MESH:D021081), genital tract infection (MESH:D060737), male infertility (MESH:D007248), DFI (MESH:D012892), SDI (MESH:D009845), Bacterial infection (MESH:D001424), Dysfunction (MESH:D006331)
- **Chemicals:** potassium phosphate (MESH:C013216), TCA (MESH:D014238), agar (MESH:D000362), Triton X-100 (MESH:D017830), oil (MESH:D009821), MDA (MESH:D008315), LeucoScreen reagent (-), H2O2 (MESH:D006861), NaCl (MESH:D012965), H&amp;E (MESH:D006371), sodium citrate (MESH:D000077559), hematoxylin (MESH:D006416), eosin (MESH:D004801), PBS (MESH:D007854), TBARS (MESH:D017392), alcohol (MESH:D000438), HCl (MESH:D006851), formaldehyde (MESH:D005557), aniline blue (MESH:C017006), CO2 (MESH:D002245), Lipid (MESH:D008055), testosterone (MESH:D013739)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Pseudomonas aeruginosa (species) [taxon 287], Metamycoplasma hominis (species) [taxon 2098], Homo sapiens (human, species) [taxon 9606], Escherichia coli (E. coli, species) [taxon 562], Streptococcus agalactiae (species) [taxon 1311], Enterococcus faecalis (species) [taxon 1351], Ureaplasma urealyticum (species) [taxon 2130], Neisseria gonorrhoeae (species) [taxon 485]

## Full text

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## Figures

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12939281/full.md

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Source: https://tomesphere.com/paper/PMC12939281