Inhaled IL-2 induces systemic immunomodulation in patients with renal cell carcinoma and lung metastasis.
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.
Diaz
David
D
CNB-CSIC R&D Associated Unit, Department of Medicine, University of Alcalá, Madrid, Spain.
Chara
Luis
L
Chevarria
Julio
J
Carballido
Joaquin
J
Esteban
Emilio
E
Navas
Victor
V
Monserrat
Jorge
J
Prieto
Alfredo
A
de la Hera
Antonio
A
Alvarez-Mon
Melchor
M
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
D000970:Antineoplastic Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007376:Interleukin-2