In vivo regulation of transforming growth factor ?1 transcription by immunotherapy: interleukin-2 impairs interferon-?-stimulated increase in steady-state mRNA levels of transforming growth factor ?1
| Autor: | B. Jahn, J. Brieger, Lothar Bergmann, Paris S. Mitrou, K. Fenchel |
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| Rok vydání: | 1994 |
| Předmět: |
Interleukin 2
medicine.medical_specialty Cancer Research Transcription Genetic medicine.medical_treatment Lymphocyte Injections Subcutaneous Immunology Transforming Growth Factor beta Internal medicine Gene expression medicine Cytotoxic T cell Humans Immunology and Allergy RNA Messenger Carcinoma Renal Cell Melanoma Interferon alfa Cells Cultured business.industry Immunotherapy Blotting Northern Kidney Neoplasms Recombinant Proteins Cytokine Endocrinology medicine.anatomical_structure Oncology Injections Intravenous Interferon Type I Cancer research Leukocytes Mononuclear Autoradiography Interleukin-2 business medicine.drug Transforming growth factor Densitometry |
| Zdroj: | Cancer Immunology, Immunotherapy. 38:304-310 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s002620050070 |
| Popis: | Recombinant interleukin-2 (rIL-2) in combination with recombinant interferon alpha (rIFN alpha) has been shown to mediate significant antitumoral effects in some patients with advanced renal cell cancer or malignant melanoma. The therapeutic effects may be partially modulated by secondarily induced cytokines, especially with regard to in vivo lymphocyte activation. To investigate possible negative effects on lymphocyte activation during immunotherapy, we designed a study on transcription of transforming growth factor beta 1 (TGF beta 1), a known inhibitor of lymphocyte function, in patients undergoing treatment with daily alternating administration of rIFN alpha and rIL-2. Here we present data on gene expression of TGF beta 1. Kinetic mRNA studies revealed an increase of TGF beta 1 mRNA in peripheral mononuclear cells 12 h after subcutaneous injection of rIFN alpha. The following intravenous rIL-2 administration significantly decreased the amounts of TGF beta 1-specific mRNA. In contrast to the effect of the first dose, subsequent application of rIFN alpha did not enhance TGF beta gene expression during rIFN alpha/IL-2 therapy. The diminished TGF beta 1 gene expression returned to pretreatment levels 1-7 days after the last rIL-2 administration. When concomitant with a decrease in TGF beta 1 transcripts. Our results indicate a complex regulatory effect on secondarily induced cytokines such as TGF beta 1 by immunotherapeutic approaches. The rIL-2-mediated down-regulation of increased TGF beta 1 steady-state mRNA levels following rIFN alpha may represent a positive immune regulatory effect on cytotoxic cells. Furthermore this effect may modulate proliferation of neoplastic tissues. |
| Databáze: | OpenAIRE |
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