Synergic in vitro effects of interleukin-2 and tau-interferon on the migration of blood monocytes from control subjects and patients with lung cancer.
BACKGROUND
Macrophages can play a major role against cancer by exerting their cytotoxic activity against tumor cells. The presence of macrophages in tumor stroma is related to the recruitment of circulating blood monocytes through the release of chemotactic factors by cancer cells. However, fewer blood monocytes from patients with cancer, such as lung cancer, migrate from in vivo and in vitro, compared with blood monocytes control subjects.


METHODS
Two cytokines, interleukin-2 (IL-2) and tau-interferon (tau-INF), proposed in the treatment of cancer, were tested for their ability to modulate the migratory response in modified Boyden chemotactic chambers of blood monocytes obtained from control subjects and patients with lung cancer in the presence of two chemotactic factors: N-formylmethionyl-leucyl-phenylalanine and complement fraction C5a (C5a).


RESULTS
Incubation with IL-2 and tau-INF resulted in a dose-dependent depression of the migration of blood monocytes from control subjects and patients with lung cancer. IL-2 depression was induced by IL-2 concentrations of 10(5) units/ml, and tau-IFN effects were measured for concentrations of 100 mu/ml. Furthermore, when low concentrations of IL-2 were tested in combination with low concentrations of tau-IFN, dose-dependent depression of blood monocyte migration occurred.


CONCLUSIONS
Dose-dependent depression of blood monocyte migration may modulate the inflammatory component of tumor stroma in patients with lung cancer treated with these cytokines. It may also explain, in part, the high incidence of infections in patients treated with IL-2.
Inserm Unité 14, Vandoeuvre-les-Nancy, France.
P
P
Vaillant
N
N
Martinet
Y
Y
Martinet
D000230:Adenocarcinoma / Q000097:blood; D000328:Adult; D018288:Carcinoma, Small Cell / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D003864:Depression, Chemical; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology
D007376:Interleukin-2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D007371:Interferon-gamma