Vitamin D3 Toxicity-Induced Hypercalcemia in Staphylococcal Arthritis: A Focus on IL-6

Background: Vitamin D3  over-supplementation can induce toxicity through the development of hypercalcemia and may disturb immune modulation. This study examines the relationship between hypercalcemia  resulting from Vitamin D3 Overdose and serum Interleukin-6 (IL-6) levels in patients diagnosed with staphylococcal arthritis.
Methods: Forty male patients (mean age: 31 years; range: 17–45 years) were enrolled from Dec. 2024 to Feb. 2025. Twenty cases of staphylococcal arthritis were compared with twenty healthy male controls. Serum concentrations of Vitamin D3, calcium, IL-6, and other biochemical markers (urea, creatinine, ESR, WBC, and potassium) were analyzed. Staphylococcus aureus was isolated from synovial fluid and confirmed using the Vitek 2 system.
Results: Vitamin D3 levels were significantly elevated in patients (498.95 ± 247.43 ng/mL) compared to controls (34.6 ± 17.7 ng/mL, p < 0.001). Calcium levels were also significantly higher in the patient group (15.72 ± 2.61 mg/dL) compared to the control group (9.2 ± 0.5 mg/dL, p < 0.001). Conversely, IL-6 levels were markedly reduced in patients (4.07 ± 2.02 pg/mL) compared to controls (10.2 ± 1.3 pg/mL, p < 0.001), indicating an immunosuppressive profile. Other laboratory markers (urea, creatinine, ESR, WBC, potassium) also showed statistically significant differences (p < 0.05). Pearson correlation revealed a strong negative association between Vitamin D3 and IL-6 levels (r = −0.97).
Conclusion: The findings demonstrate that Vitamin D3 overdose, resulting in hypercalcemia, significantly suppresses IL-6 expression in patients with staphylococcal arthritis. This suppression is mediated indirectly through hypercalcemia rather than a direct effect of Vitamin D3. Therefore, careful monitoring and individualized dose adjustment are recommended to prevent toxicity and associated immune dysregulation