Adoptive immunotherapy of human cancer: the cytokine cascade and monocyte activation following high-dose interleukin 2 bolus treatment.
Serum concentration kinetics of gamma-interferon (IFN-gamma), neopterin, 2'-5' A synthetase and tumor necrosis factor alpha were determined in five cancer patients undergoing adoptive immunotherapy with high-dose interleukin 2 (IL-2) bolus infusion and lymphokine-activated killer cells according to the National Cancer Institute, NIH protocol. In all cases a significant increase of these markers was observed after IL-2 treatment. This suggests that the antitumor effect of high-dose IL-2 bolus administration may be in part mediated by activation of a cascade of endogenous cytokines including IFN-gamma and tumor necrosis factor alpha. After IL-2 bolus injection, the kinetics of neopterin was similar but delayed when compared to that of IFN-gamma: this suggests that macrophages, the specific source of neopterin, become activated by IFN-gamma following IL-2-mediated lymphocyte induction, thus implying a possible role for macrophages in the antitumor effects mediated by IL-2 and lymphokine-activated killer cells.
Boccoli
G
G
Department of Hematology and Oncology, Istituto Superiore di Sanità, Rome, Italy.
Masciulli
R
R
Ruggeri
E M
EM
Carlini
P
P
Giannella
G
G
Montesoro
E
E
Mastroberardino
G
G
Isacchi
G
G
Testa
U
U
Calabresi
F
F
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002478:Cells, Cultured; D006801:Humans; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008262:Macrophage Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D019798:Neopterin; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase