Independent expression of p55 and p75 interleukin-2 receptors (IL-2R) during intravenous or subcutaneous administration of recombinant interleukin-2 (rIL-2) by T-lymphocytes and natural killer cells.
BACKGROUND
The effects of immunotherapy with recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes have been a matter of debate. In this study the authors addressed the issue of the biologic effects of two different schedules of rIL-2 administration (i.e., continuous intravenous infusion versus subcutaneous injection) on the expression of the p55 and p75 chains of interleukin-2 receptor (IL-2R).


METHODS
Sixteen patients were studied: 6 patients with a previous diagnosis of acute leukemia entered the study at least +60 days (+63(-)+144 days) after autologous bone marrow transplantation and were treated with continuous rIL-2 infusion; 10 patients with advanced metastatic renal cancer were treated with subcutaneous rIL-2 therapy. In both groups of patients, therapy consisted of two cycles of 5-day rIL-2, and immunologic evaluation was performed two days after completion of the second cycle.


RESULTS
Intravenous treatment was associated with a marked increase in CD56+ natural killer (NK) cells expressing the p75 but lacking the p55 IL-2R; however, the absolute number of CD3+ lymphocytes was unchanged, and they showed a low or absent expression of the p55 and negativity for the p75 IL-2R. After subcutaneous rIL-2 therapy, a slight increase in the percentage of NK cells expressing only the p75 IL-2R was shown. CD3+ lymphocytes still retained the p75 IL-2R negative phenotype, however, with a significant increase (> 15%) in p55 IL-2R expression. The absolute number of CD3+ lymphocytes was also significantly increased. Functional tests on the purified CD3+ population indicate that these cells exhibited low values of cytotoxic and proliferative activities in vitro.


CONCLUSIONS
The authors' data point out that subcutaneous administration of rIL-2 during a 2-week period is associated with a marked increase in T-cells that bear the low affinity p55 IL-2R. These findings could be relevant considering the independent role of lymphokine modulation mediated by the p55 and p75 IL-2R on T- and NK cells.
Zambello
R
R
Padua University School of Medicine, Department of Clinical Medicine, Italy.
Trentin
L
L
Cerutti
A
A
Enthammer
C
C
Milani
A
A
Franceschi
T
T
Messina
C
C
Cetto
G L
GL
Agostini
C
C
Semenzato
G
G
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D016130:Immunophenotyping; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000187:drug effects* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D007155:Immunologic Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins