Clinical trial of natural human lymphocyte-derived interleukin 2 in cancer patients: effects on cytokine production and suppressor cell status.
Lymphocyte-derived, natural, glycosylated interleukin 2 (IL 2) may have different effects in vivo than the non-glycosylated recombinant IL 2 hitherto employed in clinical trials. To test this, 9 tumor patients were given 3-6 x 10(6) U/day natural IL 2 by continuous infusion for 5 days. Compared with previously published results obtained using recombinant IL 2, as far as similar tests were performed, no unexpected results were obtained with natural IL 2 in the present study. Plasma TNF-alpha levels increased considerably during therapy, IFN-gamma very slightly, whereas IL 2-stimulated secretion of either cytokine in vitro fluctuated greatly. CD16+ and CD25+ cells increased and CD45R+ cells decreased after treatment, consistent with significant lymphocyte activation in vivo. MHC-unrestricted cytotoxicity increased after treatment. The level of CD8+ cells was and remained within the normal range, although suppressive activity generated in mixed lymphocyte culture was deficient prior to therapy. Interestingly, this normalised after therapy. These results extend studies of immunological monitoring of patients receiving IL 2, based on the first trial using natural rather than recombinant IL 2.
Pawelec
G
G
Second Department of Internal Medicine, University Medical Clinic, Tübingen, Germany.
Lenz
H J
HJ
Schneider
E
E
Bühring
H J
HJ
Rehbein
A
A
Baumgärtner
P
P
Ehninger
G
G
D003602:Cytotoxicity, Immunologic; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007155:Immunologic Factors; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma