The effect of recombinant murine interferon-gamma on the hematopoietic and immunological parameters of mice bearing metastatic Lewis lung carcinoma tumors.
The in vitro and in vivo effects of murine recombinant interferon-gamma (rIFN-gamma) on hematopoietic and immune parameters of normal mice and of mice bearing metastatic variant Lewis lung carcinoma (LLC-C3) tumors were assessed. The in vitro addition of rIFN-gamma to bone marrow or spleen cells from normal and LLC-C3-bearing mice reduced their capacity to grow into colonies in soft agar (CFU) and minimized their immune suppressive activities. In vivo studies showed that when LLC-C3 tumor-bearing mice were injected with rIFN-gamma for 2 days prior to sacrifice, there was a reduction in femoral bone marrow cellularity, CFU, and suppressor cell activity. In contrast, spleen cells of tumor-bearing mice that were injected with rIFN-gamma showed reduced blastogenesis, and increased spleen cellularity, CFU, and suppressor cell activity. Thus, short-term rIFN-gamma treatment of LLC-C3-bearing mice may be beneficial with regard to the bone marrow because it caused a decrease in hematopoiesis and suppressor cell activity, whereas it may be detrimental in the spleen because it appeared to stimulate hematopoiesis and increase splenic suppressor cell activity. The dichotomy between the in vitro versus in vivo effects of rIFN-gamma on splenic hematopoiesis and suppressor activity may be due to the stimulation of production of colony-stimulating factor (CSF) activities by spleen cells of rIFN-gamma-treated mice. Our results suggest that the tumor stimulation of hematopoiesis and its associated appearance of immune suppressor cells can be both positively and negatively altered by rIFN-gamma.
Young
M R
MR
Department of Research Services, Hines V.A. Hospital, IL 60141.
Young
M E
ME
Wepsic
H T
HT
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002452:Cell Count; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D006410:Hematopoiesis / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D007371:Interferon-gamma