In vitro modulatory effects of interleukin-3 on macrophage activation induced by interleukin-2.
BACKGROUND
The concomitant activation of macrophage-mediated immunosuppressive events might represent one of the most important biologic factors responsible for the decreased efficacy of cancer immunotherapies, including that of interleukin (IL)-2. In previous studies, the authors observed that the increase in the soluble IL-2 receptor (SIL-2R) and neopterin levels was related to the generation of macrophage-mediated immunosuppression and associated with a reduced clinical efficacy during IL-2 cancer immunotherapy. Because both cytokines and neurohormones may influence the macrophage system, the current study was done to evaluate the effects of IL-3 and of the pineal hormone melatonin (MLT) on monocyte response to IL-2 administration.


METHODS
Peripheral blood monocytes were incubated with different concentrations of IL-2, IL-3, and MLT, either alone or in association.


RESULTS
SIL-2R, neopterin, and tumor necrosis factor-alpha mean concentrations in the medium significantly increased during incubation with IL-2 at a concentration of 100 Cetus units/ml. IL-3 alone, at a dose of 10 ng/ml, also stimulated tumor necrosis factor release; no effect was found on SIL-2R and neopterin. The IL-2-induced neopterin rise was blocked by a concomitant incubation with IL-3 at a dose of 10 ng/ml. Finally, the concomitant incubation with IL-3 and MLT further inhibited neopterin release and significantly decreased IL-2-induced SIL-2R secretion.


CONCLUSIONS
These results suggest that IL-3 alone or in association with MLT may modulate macrophage functions during cancer immunotherapy with IL-2 and decrease the IL-2-induced macrophage activation.
Lissoni
P
P
Division of Radiation Oncology, San Gerardo Hospital, Milan, Italy.
Pittalis
S
S
Brivio
F
F
Tisi
E
E
Rovelli
F
F
Ardizzoia
A
A
Barni
S
S
Tancini
G
G
Giudici
G
G
Biondi
A
A
D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology; D019798:Neopterin; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D007377:Interleukin-3; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D008550:Melatonin