The systemic complement activation caused by interleukin-2/lymphokine-activated killer-cell therapy of cancer causes minimal systemic neutrophil activation.
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.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
F D
FD
Moore
D D
DD
Schoof
M
M
Rodrick
T J
TJ
Eberlein
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
D007376:Interleukin-2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003165:Complement System Proteins