Role of pro- and anti-inflammatory cytokines in diabetic neuropathy

Abstract

Background: Diabetic neuropathy (DN) is one of the most prevalent complications of type 2 diabetes mellitus, characterized by progressive peripheral nerve damage primarily resulting from chronic hyperglycaemia. Emerging evidence implicates inflammation as a key contributor to its pathogenesis. Pro-inflammatory cytokines such as IL-2, TNF-α and IL-6 promote neural injury, whereas anti-inflammatory cytokines like IL-10 and IL-4 may exert neuroprotective effects. This study aims to evaluate the serum levels of selected pro-inflammatory (IL-2, TNF-α, IL-6) and anti-inflammatory (IL-10, IL-4) cytokines in patients with diabetic neuropathy and to analyse their correlation with neuropathy severity.

Methods: A prospective, observational case control study was conducted involving 80 participants, comprising 40 diabetic neuropathy patients and 40 healthy controls at Thanjavur Medical College, Thanjavur, Tamil Nadu, India during the period of June 2025 to December 2025. Demographic characteristics, biochemical parameters and serum cytokine levels including interleukin (IL)-10, IL-4, IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) were analysed. Statistical analysis was performed using SPSS version 26.0.

Results: This study results showed that, IL-6 was significantly increased in diabetic neuropathy patients (median 8.35 (3.27–22.89) pg/mL) compared with healthy controls (2.39 (2.13–3.00) pg/ml) (p=0.007). IL-10 also demonstrated a significant change between groups (p=0.0003). No significant differences were observed for IL-4, IL-2 and TNF-α levels. Correlation analysis revealed that no significant association between HbA1c and cytokine levels. ROC curve analysis demonstrated that IL-10 exhibited the greatest diagnostic performance with an AUC of 0.882, followed by IL-6 with an AUC of 0.784.

Conclusions: The findings of the present analysis indicate that inflammatory dysregulation is associated with diabetes neuropathy patients. IL-6 and IL-10 emerged as the most significant potential cytokines and demonstrated promising diagnostic utility. These biomarkers may serve as valuable indicators of inflammation in diabetic patients and may contribute to the development of future diagnostic and therapeutic strategies. Further studies with larger sample sizes are warranted to validate these study findings.