Induction of interleukin 3 and tumor resistance by SSM, a cancer immunotherapeutic agent extracted from Mycobacterium tuberculosis.
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.
Sasaki
H
H
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Schmitt
D
D
Hayashi
Y
Y
Pollard
R B
RB
Suzuki
F
F
D000818:Animals; D004351:Drug Resistance; D006119:Groin; D015552:Injections, Intralesional; D007377:Interleukin-3 / Q000032:analysis / Q000096:biosynthesis*; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology; D008351:Mannans / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000188:drug therapy; D009500:Neutralization Tests
D007377:Interleukin-3; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama