TY - JOUR
T1 - The systemic complement activation caused by interleukin‐2/lymphokine‐activated killer‐cell therapy of cancer causes minimal systemic neutrophil activation
AU - Moore, Francis D.
AU - Schoof, Deric D.
AU - Rodrick, Mary
AU - Eberlein, Timothy J.
PY - 1991/10/21
Y1 - 1991/10/21
N2 - Twenty‐three cancer patients undergoing therapy with interleukin‐2 and lymphokine‐activated killer cells were studied for evidence of complement activation and systemic neutrophil activation occurring during the course of therapy. Patient plasma samples demonstrated evidence of marked complement activation, with 3‐fold elevations of C3a desArg concentrations by the 8th day of therapy. Concentrations of C4a desArg were also elevated by the end of therapy. In vitro chemotaxis of patients' neutrophils both to C5a and to the synthetic peptide chemotaxin, FMLP, was initially normal and then fell progressively to 60% of normal by the end of treatment. Mean neutrophil cell‐surface expression of complement receptor Type 1 and complement receptor Type 3 increased in inverse temporal relationship to the deficit in chemotaxis, but showed no consistent pattern for individuals and was only doubled at maximum. Thus, despite a degree of complement activation which should have produced pronounced neutrophil activation, the response of the circulating neutrophils was diminished. In view of this discrepancy, the toxicity of this therapy may not be mediated by activation of circulating neutrophils.
AB - Twenty‐three cancer patients undergoing therapy with interleukin‐2 and lymphokine‐activated killer cells were studied for evidence of complement activation and systemic neutrophil activation occurring during the course of therapy. Patient plasma samples demonstrated evidence of marked complement activation, with 3‐fold elevations of C3a desArg concentrations by the 8th day of therapy. Concentrations of C4a desArg were also elevated by the end of therapy. In vitro chemotaxis of patients' neutrophils both to C5a and to the synthetic peptide chemotaxin, FMLP, was initially normal and then fell progressively to 60% of normal by the end of treatment. Mean neutrophil cell‐surface expression of complement receptor Type 1 and complement receptor Type 3 increased in inverse temporal relationship to the deficit in chemotaxis, but showed no consistent pattern for individuals and was only doubled at maximum. Thus, despite a degree of complement activation which should have produced pronounced neutrophil activation, the response of the circulating neutrophils was diminished. In view of this discrepancy, the toxicity of this therapy may not be mediated by activation of circulating neutrophils.
UR - http://www.scopus.com/inward/record.url?scp=0026052449&partnerID=8YFLogxK
U2 - 10.1002/ijc.2910490405
DO - 10.1002/ijc.2910490405
M3 - Article
C2 - 1917149
AN - SCOPUS:0026052449
SN - 0020-7136
VL - 49
SP - 504
EP - 508
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -