Eosinophils activation in post-autologous bone marrow transplanted patients treated with subcutaneous interleukin-2 and interferon-alpha 2A immunotherapy.
We evaluated eosinophils morphology, physical properties and antileukemic activity in autologous bone marrow transplanted (ABMT) patients treated with subcutaneous recombinant interleukin 2 (rIL-2) and recombinant human interferon alpha 2a (IFN alpha) given as outpatient immunotherapy. All patients receiving rIL-2/IFN alpha therapy developed peripheral blood eosinophilia of 20-40% peaking at 2-4 weeks of therapy. While on rIL-2/IFN alpha therapy the eosinophils became hypodense and hypersegmented. The antibody dependent cell-mediated cytotoxic activity (ADCC) of the eosinophils against the human B-cell lymphoma cell line (Raji) was depressed post-ABMT. Prolonged (28 days) in vivo rIL-2/IFN alpha immunotherapy enhanced ADCC activity of the eosinophils and brought them to normal levels. Similarly, rIL-2/IFN alpha immunotherapy enhanced the depressed cytotoxic activity of neutrophils post-ABMT to normal levels. Thus, eosinophils and neutrophils from rIL-2/IFN alpha-treated ABMT recipients may be targeted toward tumor cells by antibody, and express tumoricidal activity. No effect of rIL-2/IFN alpha was observed on monocyte-dependent ADCC activity which remained normal post-ABMT. We conclude that in addition to their effect on lymphocytes, cytokine-mediated immunotherapy consisting of subcutaneous low doses of riL-2 and IFN alpha may mediate their therapeutic effects in cancer therapy by increasing the number of eosinophils and enhancing the antitumor activity of eosinophils and neutrophils, provided that tumor-specific or tumor-associated antibodies are present.
Fabian
I
I
Department of Histology and Cell Biology, Sackler School of Medicine, Tel Aviv University, Israel.
Kravtsov
V
V
Elis
A
A
Gurevitch
O
O
Ackerstein
A
A
Slavin
S
S
Nagler
A
A
D000293:Adolescent; D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002648:Child; D003131:Combined Modality Therapy; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006689:Hodgkin Disease / Q000097:blood / Q000276:immunology / Q000628:therapy; D006801:Humans; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007938:Leukemia / Q000097:blood / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000276:immunology / Q000628:therapy; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor