title: Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival.
abstract: BACKGROUND
  Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD).
  
  
  METHODS
  Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10.
  
  
  RESULTS
  Among healthy adult volunteers serum IL-10 levels ranged from 4.8-9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels > or = 10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, serum beta 2-microglobulin > or = 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population.
  
  
  CONCLUSIONS
  Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.
authors.affiliation: Department of Lymphoma-Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, USA. asarris@notes.mdacc.tmc.edu
authors.forename: A H
authors.initials: AH
authors.lastname: Sarris
authors.forename: K O
authors.initials: KO
authors.lastname: Kliche
authors.forename: P
authors.initials: P
authors.lastname: Pethambaram
authors.forename: A
authors.initials: A
authors.lastname: Preti
authors.forename: S
authors.initials: S
authors.lastname: Tucker
authors.forename: C
authors.initials: C
authors.lastname: Jackow
authors.forename: O
authors.initials: O
authors.lastname: Messina
authors.forename: W
authors.initials: W
authors.lastname: Pugh
authors.forename: F B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: P
authors.initials: P
authors.lastname: McLaughlin
authors.forename: M A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: J
authors.initials: J
authors.lastname: Romaguera
authors.forename: H
authors.initials: H
authors.lastname: Fritsche
authors.forename: T
authors.initials: T
authors.lastname: Witzig
authors.forename: M
authors.initials: M
authors.lastname: Duvic
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006689:Hodgkin Disease / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D016753:Interleukin-10