In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: Studies at effector and target cell level

L. Bonmassar, S. D'atri, M. Turriziani, A. Giuliani

Research output: Contribution to journalArticlepeer-review

Abstract

It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. the results show that: (a) EFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the NK function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effectors; (d) however a net "therapeutic gain" was found if the overall influence of MTBA + IFN on target and effector cells is considered.

Original languageEnglish
Pages (from-to)695-715
Number of pages21
JournalImmunopharmacology and Immunotoxicology
Volume16
Issue number4
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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