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Induction of TH1- and TH2-associated cytokine mRNA in mouse bladder following intravesical growth of the murine bladder tumor MB49 and BCG immunotherapy

  • Original Articles
  • Cytokine mRNA, Type I Response, Type II Response, Interleukin-4, Interferon γ, Murine Bladder Tumor
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Abstract

Productive immunity to murine and human parasites is associated with the development of a type I T cell response (interferon-γ-producing) while type II responses (interleukin-4-producing) suppress the development of delayed-type hypersensitivity (DTH) and the elimination of the parasite. To determine if a similar regulatory pathway might exist in tumor systems and may be effected by immunotherapeutic manipulation, we have studied the localized cytokine response to the murine bladder tumor MB49 growing intravesically in syngeneic mice. Intravesical growth of MB49 results in the host-derived expression of mRNA for both interleukin-4 (IL-4) (TH2) and interferon γ (IFNγ) (TH1), as well as tumor necrosis factor α (TNFα) expression of indeterminate origin. Intravesical instillation of bacillus Calmette-Guérin (BCG), highly effective in eliminating bladder tumors clinically and in experimental systems, results in IFNγ and TNFα mRNa production in the bladder wall, but no IL-4. Following BCG treatment of intravesical MB49, the number bladders expressing IL-4 mRNA decreases, while IFNγ and TNFα expression remains constant. These results are consistent with the mechanism of action of BCG involving the generation of an enhanced TH1 immune milieu in the bladder wall, which may contribute to the generation of productive tumor-specific immunity.

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Authors and Affiliations

  1. Division of Neoplastic Diseases, Department of Medicine, Thomas Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1014, 9107, Philadelphia, PA, USA

    Edmund C. Lattime

  2. Department of Urology, Thomas Jefferson Medical College of Thomas Jefferson University, Philadelphia, USA

    Leonard G. Gomella

  3. Immunology Program, Thomas Jefferson Medical College of Thomas Jefferson University, Philadelphia, USA

    Kathleen M. McAveney

Authors
  1. Kathleen M. McAveney
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  2. Leonard G. Gomella
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  3. Edmund C. Lattime
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Additional information

Supported by USPHS grant CA-42908. K.M.M. is the recipient of Foerderer and N. S. E. Predoctoral Fellowships. Presented in part at the American Association for Cancer Research, April 1993 and May 1994

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McAveney, K.M., Gomella, L.G. & Lattime, E.C. Induction of TH1- and TH2-associated cytokine mRNA in mouse bladder following intravesical growth of the murine bladder tumor MB49 and BCG immunotherapy. Cancer Immunol Immunother 39, 401–406 (1994). https://doi.org/10.1007/BF01534428

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  • DOI: https://doi.org/10.1007/BF01534428

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