lipoteichoic-acid and Lymphoma

Dogs with lymphoma have altered innate immunity and little is known about the effects of chemotherapy on innate immune function in dogs. Lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) - induced leukocyte cytokine production capacity, and phagocytosis and respiratory burst were evaluated in dogs prior to and following 6 weeks of chemotherapy. Dogs had decreased TNF production following LPS stimulation and increased IL-10 production following PG stimulation, which did not improve following remission of lymphoma. Dogs also had reduced E. coli-induced respiratory burst function after chemotherapy induced complete or partial remission. Dogs with lymphoma have an imbalance in pro-and anti-inflammatory cytokine production which did not improve with remission, and, following treatment, a decrease in respiratory burst function. Altered immune responses following exposure to bacterial pathogen associated molecular pattern motifs and bacteria may have many implications in the management of canine lymphoma.

Topics: Animals; Antineoplastic Agents; Cytokines; Dog Diseases; Dogs; Drug Therapy; Escherichia coli; Follow-Up Studies; Immunity, Innate; Interleukin-10; Leukocytes; Lipopolysaccharides; Lymphoma; Peptidoglycan; Phagocytosis; Remission Induction; Respiratory Burst; Teichoic Acids

We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Apoptosis; Chromatography, Affinity; Drug Screening Assays, Antitumor; Fas Ligand Protein; fas Receptor; Female; Fibrosarcoma; Interleukin-12; Interleukin-18; Killer Cells, Natural; Lipopolysaccharides; Lymphokines; Lymphoma; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Moloney murine leukemia virus; Neoplasm Transplantation; Penicillin G; Perforin; Picibanil; Pore Forming Cytotoxic Proteins; Spleen; Streptococcus pyogenes; Teichoic Acids; Th1 Cells; Th2 Cells; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha