ABSTRACT
AIM: To study in vivo efficacy of combined administration of cancer vaccine (CV), interferon (IFN) and inducer of endogenous IFN - amixin. MATERIALS AND METHODS: Sarcoma-37 cells were transplanted to female Balb/c mice. For the treatment, CV prepared from sarcoma-37 cells with the use of cytotoxic lectines from B. subtilis B-7025, murine IFN and amixin or their combinations were used. IFN production, content of circulating immune complexes and level of specific IgG antibodies in blood serum were determined by standard immunologic methods. RESULTS: Using solid form of sarcoma-37 it has been shown that introduction of IFN and amixin significantly elevated efficacy of vaccine therapy, in particular index of tumor growth inhibition reach 89.2% and 81.7%. Upon combined use of CV and IFN or CV and amixin (25 mg/kg) respectively. Significant prolongation of average life span of the animals treated with CV and IFN or CV and amixin (25 mg/kg) has been registered (up to 92.7 -/+ 10.4 and 95.0 -/+ 6.2 days respectively, vs 46.8 -/+ 1.5 days for control animals). CONCLUSION: Obtained results have shown expediency of the development of schemes for combined introduction of CV with exogenous IFN, and with inducer of endogenous IFN (amixin) for elevation of efficacy of vaccine therapy.
Subject(s)
Cancer Vaccines/immunology , Immunotherapy/methods , Interferon Inducers/administration & dosage , Interferons/administration & dosage , Sarcoma/drug therapy , Tilorone/administration & dosage , Animals , Cancer Vaccines/therapeutic use , Female , Interferon Inducers/immunology , Interferons/immunology , Mice , Mice, Inbred BALB C , Tilorone/immunologyABSTRACT
Immunotropic properties of the interferon-inducing molecular complex (MC) yeast RNA--tilorone hydrochloride have been under study. MC was experimentally studied in vivo to establish its influence on the amount of antibody-forming cells and the level of antibody formation. The influence of MC on the oxygen-generating activity of spleen macrophages was established in the HCT test. MC in a dose of 1.25 mg/kg was shown to considerably activate immunocompetent cells, thus producing pronounced influence on humoral immunity. In addition, the study showed the dose dependence of the influence of MC on individual elements of the immune system as well as differences in the dynamics of immunomodulation caused by the use of high and low doses of MC. The data thus obtained made it possible to regard MC as a promising immunomodulator.
Subject(s)
Anti-Inflammatory Agents/immunology , Hypersensitivity, Delayed/immunology , RNA, Fungal/immunology , Tilorone/immunology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/isolation & purification , Antibody-Producing Cells/cytology , Cell Count , Dose-Response Relationship, Immunologic , Down-Regulation , Drug Combinations , Injections, Intraperitoneal , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Oxygen/metabolism , Phagocytosis/immunology , RNA, Fungal/administration & dosage , RNA, Fungal/isolation & purification , Spleen/immunology , Spleen/metabolism , Tilorone/administration & dosage , Tilorone/isolation & purification , Time Factors , Up-RegulationABSTRACT
Indices were studied for cell-bound immunity during administration of a multimodality therapy treatments with making use of amiksin in patients with glial tumours of the brain IV degree anaplasia. Processes of lymph formation and differentiation of lymphocytes into natural killer cells have been found out to return to normal. No total stimulating action was recorded of the drug that would lead to stimulation of progressive growth of gliomas.
Subject(s)
Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Interferon Inducers/therapeutic use , Tilorone/therapeutic use , Brain Neoplasms/immunology , Brain Neoplasms/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Glioblastoma/immunology , Glioblastoma/surgery , Humans , Immunity, Cellular/drug effects , Interferon Inducers/immunology , T-Lymphocyte Subsets/immunology , Tilorone/immunologyABSTRACT
A synthetic muramyldipeptide (MDP) and two analogues, B30-MDP and MDP-Lys(L18), augmented serum interferon (IFN) production in mice by the inducers lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly I:C), and also augmented immune IFN production induced by purified protein derivative (PPD) in mycobacteria-sensitized mice. These compounds were most effective when administered to mice one day before the interferon inducer. By contrast, IFN production in mice by either oral tilorone or virus infection was not enhanced with these compounds. Since LPS and poly I:C are well known as early-type IFN inducers, and tilorone and virus infection are late-type inducers, we presume that MDP and its analogues are able to augment only early-type IFN production. This enhancing effect may be mediated by macrophage activation. In vivo antiviral activity of MDP and its analogues was further tested in mice infected with vaccinia virus (VV) using early-type inducers. When mice previously treated with MDP or its analogues were stimulated for IFN production with a low dose of LPS, protective activity against VV infection was markedly enhanced.
Subject(s)
Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives , Acetylmuramyl-Alanyl-Isoglutamine/pharmacology , Interferon Inducers/pharmacology , Interferons/biosynthesis , Acetylmuramyl-Alanyl-Isoglutamine/immunology , Animals , Cell Line , Female , Interferon-gamma/biosynthesis , Interferons/immunology , Lipopolysaccharides/immunology , Lipopolysaccharides/pharmacology , Macrophage Activation , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Poly I-C/immunology , Poly I-C/pharmacology , Tilorone/immunology , Tilorone/pharmacology , Vaccinia/immunology , Vaccinia/therapySubject(s)
Adjuvants, Immunologic/immunology , Benzofurans/immunology , Encephalomyelitis, Equine/microbiology , Encephalomyelitis, Venezuelan Equine/microbiology , Fluorenes/immunology , Tilorone/immunology , Vaccines, Attenuated/immunology , Animals , Antibodies, Viral/analysis , Antibody Formation , Female , Formaldehyde , Macaca mulatta , Male , MiceSubject(s)
Adjuvants, Immunologic/therapeutic use , Fluorenes/therapeutic use , Neoplasms/therapy , Propionibacterium acnes/immunology , Tilorone/therapeutic use , Animals , Chemical Phenomena , Chemistry , Diethylamines/therapeutic use , Herpesviridae Infections/pathology , Humans , Immunity , Lactate dehydrogenase-elevating virus/immunology , Lymphocyte Activation , Marek Disease/pathology , Mycoplasma Infections/pathology , Neoplasms/immunology , Neoplasms/pathology , Poultry , Simplexvirus/immunology , Tilorone/administration & dosage , Tilorone/immunologyABSTRACT
Tilorone suppressed inflammation induced by immune (direct passive Arthus reaction) as well as by non-immune agents (carrageenam-induced paw edema and abscess formation), if the compound is given 24 hr prior to the proinflammatory agonists. The non-immune anti-inflammatory effect is independent of the adrenals. A surprising findings was that total serum hemolytic complement is markedly elevated 24 hr after a single dose of tilorone.