Partial correction of defective generation of lymphokine-activated killer cells in patients with chronic myelogenous leukaemia after in vivo treatment with interferon-alpha (Wellferon).
Patients with chronic myelogenous leukaemia (CML) in untreated chronic phase are deficient in their ability to generate lymphokine-activated killer (LAK) cells from peripheral blood mononuclear cells although they possess essentially normal levels of CD16+ and Leu19+ lymphocytes, which do not seem to be actively suppressed by tumour cells. Attempts to enhance LAK cell generation in these patients are reported here. Combining the lymphokines interleukins-2, with -4 and -5 (IL-2, IL-4, IL-5), was not successful; in fact, IL-4 depressed LAK cell induction in both normal donors and CML patients. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate also failed to enhance cytotoxicity of normal donors or patients, and indomethacin was similarly without effect. The only agent found to enhance LAK cell induction by IL-2 in normal donors was interferon-gamma (but not IFN-alpha) and even this modest effect was not seen with the cells of CML patients. Increasing concentrations of IL-2 and/or culture duration also failed to improve LAK cell generation by patients. The only improvement in LAK cell generation was observed in CML patients treated for one or more months with IFN-alpha, where a steady increase of LAK activity with time after initiation of therapy was noted. These results show that the blockade of LAK cell induction in chronic-phase myelogenous leukemia patients is difficult to lift pharmacologically in vitro but possibly susceptible to biological response modifiers in vivo.
Pawelec
G
G
Immunology Laboratory, Medizinische Klinik, Tübingen, Federal Republic of Germany.
Schneider
E
E
Ehninger
G
G
Rehbein
A
A
Schmidt
H
H
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D007376:Interleukin-2; D007694:Killer Cells, Natural / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*
D007370:Interferon Type I; D007376:Interleukin-2