Myelopoiesis-associated suppressor-cell activity in mice with Lewis lung carcinoma tumors: interferon-gamma plus tumor necrosis factor-alpha synergistically reduce suppressor cell activity.
The myelopoietic stimulation which occurs in mice bearing metastatic Lewis lung carcinoma (LLC-C3) tumors is accompanied by immune suppression and the appearance of myelopoiesis-associated immune suppressor cells in the bone marrow and spleen. Low doses of recombinant murine interferon-gamma (IFN-gamma) plus recombinant human tumor necrosis factor-alpha (TNF-alpha) were used to limit myelopoiesis and, in turn, reduce the presence of myelopoiesis-associated immune suppressor cells in LLC-C3 tumor bearers. Neither IFN-gamma nor TNF-alpha alone had any effect in vitro on the growth of myeloid progenitor cells into colonies or on the suppressive activity of bone-marrow cells from LLC-C3-bearing mice. However, the combination of low doses of IFN-gamma and TNF-alpha synergistically inhibited both the growth of myeloid progenitor cells into colonies and the suppressive activity of bone-marrow cells from tumor-bearers. Similar results were obtained in vivo. When used alone, neither IFN-gamma nor TNF-alpha had any effect on myelopoiesis or on suppressor-cell activity. When combined, IFN-gamma plus TNF-alpha synergistically suppressed myelopoiesis and the presence of immune suppressive cells both in the bone marrow and in the spleen of tumor bearers. T-lymphocyte blastogenic and NK cytotoxic activities of the tumor-bearers were restored only after treatment with both IFN-gamma and TNF-alpha.
Young
M R
MR
Department of Research Services, Hines V.A. Hospital, IL 60141.
Young
M E
ME
Wright
M A
MA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D003114:Colony-Forming Units Assay; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma