Immunomodulatory properties of recombinant murine and human tumor necrosis factor.
Tumor necrosis factor has traditionally been thought to have direct cytostatic and cytotoxic properties with little or no direct immunomodulatory activity. We report here that tumor necrosis factor is able to activate macrophages both in vitro and in vivo and can increase a mixed lymphocyte response and act as an adjuvant for both T- and B-cells in vivo. Adjuvant activity in T-cells occurred in conjunction with the administration of a suboptimal syngeneic tumor cell vaccine. In addition, tumor necrosis factor demonstrated a potent dose-dependent effect on bone marrow stem cell number, dramatically depressing cellularity and thus total stem cell number. An appreciable interval is required for recovery from such stem cell depletion. Therefore, the study of the therapeutic activity of tumor necrosis factor must include a consideration of its immunomodulatory properties.
Talmadge
J E
JE
Preclinical Screening Laboratory, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Phillips
H
H
Schneider
M
M
Rowe
T
T
Pennington
R
R
Bowersox
O
O
Lenz
B
B
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha