title: Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.
abstract: Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG-CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: J
authors.initials: J
authors.lastname: Rabinowitz
authors.forename: W P
authors.initials: WP
authors.lastname: Petros
authors.forename: A R
authors.initials: AR
authors.lastname: Stuart
authors.forename: W P
authors.initials: WP
authors.lastname: Peters
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000502:physiology; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine