title: Inhaled IL-2 induces systemic immunomodulation in patients with renal cell carcinoma and lung metastasis.
abstract: The peripheral blood lymphocytes of eight patients with metastatic renal cell carcinoma, and of eight healthy volunteers were analyzed by four-color flow cytometry to characterize the immunophenotypic alterations manifested, determine the prevalence of lymphocyte apoptosis, and detect evidence of the systemic effect of inhaled IL-2. The T, B and NK lymphocytes of untreated patients were found to have undergone profound changes characterized by an increase in susceptibility to both spontaneous and mitogen-induced ex vivo apoptosis, a modified distribution of the main lymphocyte populations in the peripheral blood, and alterations in activation status. An increase in the proportion of regulatory T cells was also seen in these patients. Treatment with inhaled IL-2, however, normalized the rate of apoptosis in all the lymphocyte subpopulations studied, as well as their distribution and activation status. These findings demonstrate that inhaled IL-2 has systemic immunomodulatory effects.
authors.affiliation: CNB-CSIC R&D Associated Unit, Department of Medicine, University of Alcalá, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Diaz
authors.forename: Luis
authors.initials: L
authors.lastname: Chara
authors.forename: Julio
authors.initials: J
authors.lastname: Chevarria
authors.forename: Joaquin
authors.initials: J
authors.lastname: Carballido
authors.forename: Emilio
authors.initials: E
authors.lastname: Esteban
authors.forename: Victor
authors.initials: V
authors.lastname: Navas
authors.forename: Jorge
authors.initials: J
authors.lastname: Monserrat
authors.forename: Alfredo
authors.initials: A
authors.lastname: Prieto
authors.forename: Antonio
authors.initials: A
authors.lastname: de la Hera
authors.forename: Melchor
authors.initials: M
authors.lastname: Alvarez-Mon
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D001239:Inhalation / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007376:Interleukin-2