Interleukin-2 therapy enhances salicylate oxidation by blood granulocytes
AL Sagone , RM Husney, PL Triozzi and J Rinehart
Division of Hematology and Oncology, Ohio Stat University, Columbus 43210.
These studies determined the effect of interleukin-2 (IL-2) immunotherapy
on the oxidative metabolism of the blood granulocytes of eight patients
with metastatic renal cancer. We quantitated the rate of the hexose
monophosphate shunt activity (HMPS), hydrogen peroxide (H2O2) production,
and salicylate oxidation of the unstimulated and phorbol myristate acetate
(PMA)-stimulated granulocyte cultures before, during, and after a 5-day
continuous infusion of IL-2. There was no change in the rate of HMPS
activity. However, the rate of salicylate oxidation of the unstimulated and
PMA-stimulated cultures of these patients was significantly increased after
the therapy was complete. Overall, there was no increase in the rate of
H2O2 production, although the PMA-stimulated cultures of three of eight
patients had a twofold higher production of H2O2 after treatment compared
with the pretreatment values. The enhanced rate of salicylate oxidation by
the granulocytes after treatment indicates that these cells were
"stimulated" in vivo to produce a potent oxidant, which is most likely
hydroxyl radical or an oxidant of comparable activity. Further, the
granulocytes were primed ("activated"), since they had an augmented
response to PMA. IL-2 did not stimulate the oxidative metabolism of
granulocyte cultures in vitro, suggesting that the IL-2 effect in vivo is
not a direct one. Our results indicate that IL-2 immunotherapy is
associated with the activation of blood granulocyte oxidative metabolism
and that these activated granulocytes may be related to some of the toxic
side effects of IL-2 therapy such as the capillary leak syndrome. Further
oxidant injury to the granulocytes may explain the reported defect in
chemotaxis.
Volume 78,
Issue 11,
pp. 2931-2936,
12/01/1991
Copyright © 1991 by The American Society of Hematology
