title: Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  Alterations 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).
  
  
  METHODS
  Cytometric 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 2months after TACE in 63 evaluable patients.
  
  
  RESULTS
  Serum 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, 2months after TACE. Patients with larger tumors (>5cm) 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.
  
  
  CONCLUSIONS
  TACE 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.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Republic of Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Byong Sun
authors.initials: BS
authors.lastname: Oh
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Chung
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Jung
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Jekarl
authors.forename: Seungok
authors.initials: S
authors.lastname: Lee
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006499:Hepatic Artery / Q000473:pathology*; D006505:Hepatitis / Q000097:blood / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000637:Transaminases / Q000097:blood; D047368:Tumor Burden
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000637:Transaminases
keywords: AFP; ALT; AST; Acute-phase proteins; Cytokines; HCC; Hepatocellular carcinoma; IFN-γ; IL; Inflammation; Interleukin; PVT; T helper cell; TACE; TNF-α; Th; alanine aminotrasferase; aspartate aminotransferases; interferon-γ; interleukin; portal vein thrombosis; transarterial chemo-embolization; tumor necrosis factor-α; α-fetoprotein