Erythropoietin enhances immune responses in mice.
Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an anti-neoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.
Katz
Odelia
O
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Gil
Lidor
L
Lifshitz
Lilach
L
Prutchi-Sagiv
Sara
S
Gassmann
Max
M
Mittelman
Moshe
M
Neumann
Drorit
D
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007142:Immunoglobulin gamma-Chains / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D007145:Immunoglobulin kappa-Chains; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D004921:Erythropoietin; D006433:Hemocyanins