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Induction of interleukin 3 and tumor resistance by SSM, a cancer immunotherapeutic agent extracted from Mycobacterium tuberculosis.

Abstract
Interleukin 3 (IL-3) activity was demonstrated when inguinal lymph node cells obtained from Bacillus Calmette-Guérin-sensitized mice (BCG-ILNC) were stimulated in vitro with SSM, an immunomodulator extracted from Mycobacterium tuberculosis. The IL-3 activity was first detected on Day 1 in culture fluids of BCG-ILNC stimulated with SSM, reached a peak on Day 3, and then gradually decreased. The activity was completely neutralized by treatment with anti-murine IL-3 monoclonal antibody (mAb). When BCG-ILNC were treated with anti-Thy 1.2 or anti-Lyt 1.2 mAb followed by complement, IL-3 was not produced in the culture fluids. However, IL-3 in the culture fluids was detected when BCG-ILNC were treated with anti-Lyt 2.2 mAb, anti-asialo-GM1, or anti-mouse immunoglobulin antiserum followed by complement. These results suggested that Lyt 1+ T-cells appeared to be required for the production of IL-3 from BCG-ILNC stimulated with SSM. In addition, low but significant IL-3 activity was also observed in sera of mice treated with SSM. However, serum IL-3 activity was not detected in mice treated with both SSM and Thy 1.2 or Lyt 1.2 mAb, whereas the activity was induced by SSM in mice treated with anti-Lyt 2.2 mAb or anti-asialo-GM1 antiserum. On the other hand, the in vivo growth of IMC tumors inoculated in BALB/c x DBA/2 F1 mice was significantly decreased by intralesional injection of culture fluids containing IL-3, as well as by SSM itself. This antitumor activity of the culture fluids was not altered when it was treated with mAbs for interleukin 1, interleukin 2, or anti-mouse gamma-interferon antiserum. The antitumor activity of the fluid was only eliminated when it was treated with anti-mouse IL-3 mAb. Since nonspecific resistance to tumors in mice stimulated with SSM appears to require Lyt 1+ T-cells, these results suggest that, in part, nonspecific resistance to tumors of mice stimulated with SSM may be developed through IL-3, which was produced by Lyt 1+ T-cells after SSM stimulation.
AuthorsH Sasaki, D Schmitt, Y Hayashi, R B Pollard, F Suzuki
JournalCancer research (Cancer Res) Vol. 50 Issue 13 Pg. 4032-7 (Jul 01 1990) ISSN: 0008-5472 [Print] United States
PMID2354453 (Publication Type: Journal Article)
Chemical References
  • Interleukin-3
  • Lipids
  • Mannans
  • specific substance maruyama
Topics
  • Animals
  • Drug Resistance
  • Groin
  • Injections, Intralesional
  • Interleukin-3 (analysis, biosynthesis)
  • Lipids (administration & dosage, pharmacology)
  • Lymph Nodes (cytology)
  • Mannans (administration & dosage, pharmacology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Neoplasms (drug therapy)
  • Neutralization Tests

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