Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma

• There are differences in cytokine levels between HCC patients and healthy controls.
• Cytokine changes during TACE are affected by hepatitis, Child class, and HCC stage.
• IL-6 and IL-22 rise early after TACE, while Th2 cytokines rise in late phase.
• Early-phase increase in IL-6 levels is associated with post-TACE hepatitis.
• Late-phase increases in Th2 cytokines imply host immune suppression in large HCC.

BackgroundAlterations in cytokine profiles after chemotherapy can affect the outcomes of cancer patients. This study evaluated the clinical implications of cytokine changes after transarterial chemo-embolization (TACE) in patients with hepatocellular carcinoma (HCC).MethodsCytometric bead immunoassays were used to simultaneously measure 13 cytokines (interleukin [IL]-12p70, interferon-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1β, and tumor necrosis factor-α) in the sera of 83 patients with HCC and 33 healthy controls. Cytokines were serially monitored at baseline, on days 3 and 7, and 2 months after TACE in 63 evaluable patients.ResultsSerum levels of IL-5, IL-6, and IL-17A were higher in patients with HCC than in healthy controls, whereas IL-1β and IL-22 levels were lower in patients with HCC. Of the cytokines measured, only the IL-6 level showed a significant positive correlation with both tumor size and Child-Pugh score. The Child-Pugh B/C group had higher IL-6 and lower IL-22 levels at baseline and exhibited relatively minor changes in cytokine levels compared with the Child-Pugh A group. We observed diverse changing patterns of individual cytokines on each date tested, with IL-6 and IL-22 increasing early after TACE. Particularly, IL-6 reached a peak on day 3 and finally decreasing on and after day 7. IL-4, IL-5, and IL-10, on the other hand, increased during the late phase, 2 months after TACE. Patients with larger tumors (>5 cm) showed a transient but significant early-phase increase in IL-6 levels coupled with severe post-TACE hepatitis, as well as late-phase increases in IL-4, IL-5, and IL-10 levels after TACE.ConclusionsTACE induces changes in levels of multiple cytokines. Distinct panels of cytokine changes are not uniform, and are influenced by treatment-induced inflammation, underlying liver function, and HCC stage. Early-phase increases in IL-6 after TACE reflect acute-phase responses and are partly associated with post-treatment hepatitis, while late-phase increases in Th2 cytokine profiles suggest immune suppression in patients with large tumors.