The administration of low doses of recombinant interleukin-2 (rIL-2) i
n vivo to patients with malignant neoplasms has been demonstrated to s
electively increase the number of circulating natural killer (NK) cell
s in these patients. Recent evidence from SCID mouse models suggests t
hat IgG subclass levels can be influenced by the presence and activity
of NK cells. Therefore, we sought to examine the effect of rIL-2 infu
sions on human serum IgG subclass concentrations. We determined serum
IgG subclass concentrations in 27 cancer patients receiving low-dose r
IL-2 by daily continuous intravenous infusion. Eleven of these patient
s had active, metastatic, nonhematologic tumors; 16 patients had recei
ved IL-2 when they were in a minimal residual disease state after auto
logous or allogeneic bone marrow transplantation. Samples obtained bef
ore beginning IL-2 therapy and 8 to 10 weeks into therapy were tested.
Treatment with IL-2 resulted in an increase in the percentage of CD56
+ NK cells from 18% to 54% (P = .0001). A significant decrease in geom
etric mean lgG2 concentration from 2,017 mu g/mL to 1,655 mu g/mL was
noted over this time interval (P = .03). Furthermore, the geometric me
an lgG2 concentration after treatment was significantly lower than tha
t of healthy controls (P = .026). In contrast, no significant changes
in serum IgG1, IgG3, or IgG4 were noted during r-IL2 infusions. Our da
ta suggest that rIL-2 treatment selectively decreases serum lgG2 conce
ntrations. We speculate that increased NK cells mediate downregulation
of human serum IgG2. (C) 1995 by The American Society of Hematology.