title: The in vivo immunomodulatory effect of recombinant tumour necrosis factor-alpha in guinea pigs vaccinated with Mycobacterium bovis bacille Calmette-Guérin.
abstract: Previous studies from our laboratory demonstrated that treatment in vitro with recombinant guinea pig tumour necrosis factor TNF (rgpTNF)-α-enhanced T cell and macrophage functions. Similarly, injection of Mycobacterium tuberculosis-infected guinea pigs with anti-TNF-α altered splenic granuloma organization and caused inflammatory changes and reduced the cell-associated mycobacteria in the tuberculous pluritis model. In this study, rgpTNF-α was injected into bacille Calmette-Guérin (BCG)-vaccinated guinea pigs to modulate immune functions in vivo. Guinea pigs were vaccinated intradermally with BCG, 2 × 10(3) colony-forming units (CFU) and injected intraperitoneally with either rgpTNF-α (25 µg/animal) or 1% bovine serum albumin (BSA) for a total of 12 injections given every other day. Treatment with rgpTNF-α significantly enhanced the skin test response to purified protein derivative (PPD), reduced the number of CFUs and increased the PPD-induced proliferation in the lymph nodes at 6 weeks after vaccination. The levels of interleukin (IL)-12 mRNA were increased in the lymph node and spleen cells stimulated with PPD. TNF-α treatment induced a decrease in TNF-α, IL-12p40 and IL-10 mRNA levels in peritoneal cells following PPD stimulation while live M. tuberculosis caused an increase in TNF-α mRNA and a decrease in the IL-10 mRNA expression. TNF-α injection also induced an increase in the infiltration of mononuclear cells and in the proportions of CD3(+) T cells in the lymph nodes. These results indicate that rgpTNF-α enhances some aspects of T cell immunity and promotes control of mycobacteria in the tissues. Future studies will address the role of TNF-α in BCG-vaccinated guinea pigs following low-dose pulmonary challenge with virulent M. tuberculosis.
authors.affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College of Medicine, College Station, TX, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Kramp
authors.forename: D N
authors.initials: DN
authors.lastname: McMurray
authors.forename: C
authors.initials: C
authors.lastname: Formichella
authors.forename: A
authors.initials: A
authors.lastname: Jeevan
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha