Modulation of macrophage response to interleukin-2 immunotherapy by interleukin-3 in cancer patients.
It has been observed that neopterin, a specific marker of macrophage activation, increases during cancer immunotherapy with IL-2, and this effect is mediated by interferons produced by IL-2-stimulated lymphocytes. Moreover, our previous studies have shown that neopterin rise during IL-2 immunotherapy is associated with an enhanced release of soluble IL-2 receptor (SIL-2R), which may suppress IL-2-dependent immune functions. This finding would suggest that neopterin increase may be related to the generation of suppressive events, which occur during IL-2 immunotherapy. On the basis of the documented modulatory effect of IL-3 on macrophage functions, we have evaluated the influence of IL-3 on neopterin secretion during IL-2 immunotherapy. The study was performed in advanced lung cancer patients. We have investigated 9 immunotherapeutic courses consisting of IL-2 (6M IU/day s.c. for 5 days/week for 3 weeks) plus IL-3 (1 microgram/(kg x day) i.v. for 14 days, starting 7 days before IL-2). The results were compared to those found during 18 courses with IL-2 alone. Mean neopterin levels increased significantly during IL-2 alone, but not in response to IL-3 plus IL-2. SIL-2R rise was significantly higher during IL-2 than during IL-3 plus IL-2. Mean numbers of NK cells and activated lymphocytes increased significantly in both groups of patients, but were significantly lower at the end of the treatment in patients receiving IL-2 alone than in those treated with IL-3 plus IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Lissoni
P
P
Division of Radiation Oncology, San Gerardo Hospital, Milan, Italy.
Rovelli
F
F
Barni
S
S
Ardizzoia
A
A
Pittalis
S
S
Tisi
E
E
Perlangeli
V
V
Tancini
G
G
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002277:Carcinoma / Q000276:immunology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007377:Interleukin-3 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D007377:Interleukin-3; D015375:Receptors, Interleukin-2; D001708:Biopterins; D019798:Neopterin