Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro.
We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Dupere
S
S
Biotherapeutics Inc., Franklin, Tennessee.
Obiri
N
N
Lackey
A
A
Emma
D
D
Yannelli
J
J
Orr
D
D
Birch
R
R
O'Connor
T E
TE
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma