title: Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin's lymphoma cells and act as cooperative growth factors.
abstract: The in vivo production of interleukin (IL)-10, IL-6, IL-2, and tumor necrosis factor (TNF)-alpha in tumor samples was investigated by immunohistochemistry in 54 non-Hodgkin's lymphomas (NHLs). Respectively, 55, 89, 23, and 29% of tumor samples were found positive for IL-10, IL-6, IL-2, and TNF-alpha expression by immunohistochemistry. Using reverse transcription-PCR, the mRNA of IL-10 and IL-6 were detectable in all samples tested and in 90 and 34% of the samples for TNF-alpha and IL-2, respectively. In 13 patients, fresh tumor tissue was available for B NHL cell purification with Dynabeads. IL-10, IL-6, IL-2, and TNF-alpha were detectable in the supernatant of 38, 100, 0, and 23% of purified tumor cell preparations (PTCPs), respectively. All patients with detectable IL-10 in culture had increased serum IL-10. IL-6 production by tumor cells and serum IL-6 levels were also found to be highly correlated (P < 0.0001). This suggests that tumor cells are a major source of serum IL-1O and IL-6 in these patients. Exogenous IL-10, IL-6, IL-2, and TNF-alpha significantly enhanced the [3H]thymidine uptake in 13 of 13 (100%), 5 of 13 (38%), 9 of 13 (69%), and 2 of 10 (20%) PTCPs costimulated with anti-CD40, respectively. IL-2, IL-6, and TNF-alpha synergized with IL-10 in 54, 23, and 30% of PTCPs. The combination of IL-10, IL-2, and IL-6 induced the maximal level of proliferation in 12 (92%) of 13 PTCPs. CD40 ligand mRNA expression was also detectable in vivo using reverse transcription-PCR in 28 of the 29 (97%) tumor samples tested, including 11 of those tested for [3H]thymidine incorporation. These results show that IL-1O, IL-6, IL-2, and TNF-alpha are produced in NHL tumors and may cooperate in vivo to increase NHL cell proliferation.
authors.affiliation: Centre Léon Bérard, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Voorzanger
authors.forename: R
authors.initials: R
authors.lastname: Touitou
authors.forename: E
authors.initials: E
authors.lastname: Garcia
authors.forename: H J
authors.initials: HJ
authors.lastname: Delecluse
authors.forename: F
authors.initials: F
authors.lastname: Rousset
authors.forename: I
authors.initials: I
authors.lastname: Joab
authors.forename: M C
authors.initials: MC
authors.lastname: Favrot
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006133:Growth Substances / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D006133:Growth Substances; D007376:Interleukin-2; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10