title: Prolongation of survival of mice bearing the Eb and ESb lymphoma by treatment with interferon inducers alone or in combination with Corynebacterium parvum.
abstract: The objective of this study was to evaluate if pretreatment with Corynebacterium parvum (C. parvum) augments the effects of interferon (IFN) inducers on survival of DBA/2 mice transplanted with two syngeneic lymphoma variants, the low metastatic Eb and the high metastatic ESb tumor. The involvement of IFN in the treatment effects was investigated. As inducers of IFN-alpha/beta Newcastle disease virus (NDV), polyinosinic-polycytidylic acid (polyI:polyC), and 10-carboxymethyl-9-acridanone (CMA) were injected i.p. at the site of tumor transplantation. The Eb tumor was found to be sensitive to the antiproliferative action of IFN-alpha/beta in vitro. In vivo single injections of each of the inducers retarded growth of the Eb tumor. In C. parvum-pretreated mice the effects of the inducers on survival were markedly increased. There was a correlation between prolonged survival and local IFN levels in response to polyI:polyC or CMA but not upon NDV. Injections of each of the inducers increased cytotoxicity of peritoneal exudate cells against the Eb tumor cells in vitro especially when mice were pretreated with C. parvum. Although other mechanisms cannot be excluded IFN-mediated activation of host defence and also direct antiproliferative effects of endogenously produced IFN seem to be involved in the antitumor effects by these IFN inducers in the Eb model. In the ESb tumor model irrespective of additional pretreatment with C. parvum survival was only slightly prolonged by the treatments and endogenous IFN induction did not result in any real benefit for the animals. When compared with Eb cells the ESb cells were less sensitive to the antiproliferative action of IFN-alpha/beta in vitro and less sensitive to in vitro cytotoxicity by the host cells. Although other mechanisms may additionally be active in vivo the different susceptibility of the Eb and ESb tumor cells to the direct and indirect actions of IFN seems to contribute to the different responsiveness of these tumor cell lines to the treatments with IFN inducers.
mesh_terms: D000166:Acridines / Q000494:pharmacology; D000818:Animals; D003602:Cytotoxicity, Immunologic; D007167:Immunotherapy; D007369:Interferon Inducers / Q000627:therapeutic use*; D007372:Interferons / Q000096:biosynthesis / Q000627:therapeutic use; D008223:Lymphoma / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009522:Newcastle disease virus / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D011070:Poly I-C / Q000627:therapeutic use; D011425:Propionibacterium acnes / Q000276:immunology*
chemical_list: D000166:Acridines; D007369:Interferon Inducers; D007372:Interferons; D011070:Poly I-C; C026430:10-carboxymethyl-9-acridanone