Interleukin-6 levels decrease following rituximab treatment but increase following tocilizumab treatment

Idiopathic multicentric Castleman disease (iMCD) is a rare, gradually progressive lymphoproliferative disorder thought to arise from chronic hypercytokinemia, with IL-6 playing a central role in disease manifestations. C-reactive protein (CRP) levels are widely used as a surrogate marker of IL-6 activity in clinical practice. Although anti-IL-6 therapies, such as tocilizumab, are established treatments for iMCD, spurious elevation of circulating IL-6 levels after IL-6 pathway blockade has been reported, complicating biomarker interpretation. In contrast, changes in IL-6 and CRP levels following rituximab therapy remain poorly characterized, and direct comparisons between these therapeutic approaches are limited. Therefore, this retrospective study measured serum IL-6 and CRP levels in 17 patients (12 men and five women; mean age, 45 years) with iMCD before and after treatment with rituximab (n = 8) and tocilizumab (n = 9). Paired t test were used to assess in-group differences. After rituximab therapy, CRP values decreased from 67.7 ± 55.5 (range: 1.0–174.9) to 25.8 ± 29.0 (range: 1.0–71.2) mg/L, while IL-6 values decreased from 25.6 ± 29.7 (range: 1.3–86.8) to 12.0 ± 11.2 (range: 0.8–31.0) pg/mL (normal range < 8.0), although these reductions were not statistically significant. In contrast, tocilizumab therapy resulted in a significant decrease in CRP values decreased from 68.9 ± 40.8 (range: 24.0–147.9) to 7.9 ± 9.8 (range: 0.1–30.5) mg/L (p < 0.05), while IL-6 levels increased from 24.2 ± 7.3 (range: 14.0–37.0) to 749.2 ± 497.7 (range: 26.5–1720.0) pg/mL (normal range < 8.0) (p < 0.05). These findings indicate distinct biomarker dynamics, in which tocilizumab therapy led to elevated IL-6 levels, while rituximab improved iMCD symptoms by reducing IL-6 levels.