A DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER THERAPY STUDY WITH NATURAL HUMAN IL-2 (NHUIL-2) IN COMBINATION WITH REGULAR INTRAVENOUS GAMMA-GLOBULIN (IVIG) INFUSIONS IN 10 PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY (CVID)

Ten CVID patients with defective IL-2 synthesis in vitro were treated with nhuIL-2 in a placebo-controlled, double blind, crossover therapy study during a period of 12 months. No severe side-effects of nhuIL-2 were recorded. Marginal serum nhuIL-2 levels were measurable in indivi dual patients only during the therapy phase. Serum levels of soluble I L-2 receptors were unaffected by the therapy. nhuIL-2 and placebo grou ps did not differ significantly with respect to requirement of IVIG su bstitutions which were performed whenever serum IgG levels dropped bel ow 5 g/l: a total of 53 IVIG infusions (corresponding to 17.6 g IgG/mo nth per patient) was necessary during the placebo phase, and 48 infusi ons (16.4 g IgG/month per patient) during the nhuIL-2 treatment phase. Thus, nhuIL-2 therapy was ineffective in improving spontaneous IgG sy nthesis in vivo. Nevertheless, the group of patients receiving nhuIL-2 during the first 6 months of the study exhibited a significant reduct ion of severe infections (n=25) during the following 6 months of place bo treatment (n=7) (P<0.045). The infection score dropped in this grou p from 181 to 23 (P < 0.015). Patients of the second group receiving f irst placebo and then nhuIL-2 did not experience a significant differe nce in number and score of infectious episodes: 25 infections were rec orded during the first 6 months and 24 during the following 6 months. We suppose that nhuIL-2 therapy of CVID patients reduces susceptibilit y to severe infections, possibly via the induction of a specific antib ody response, which is effective at the earliest 6 months after initia ting nhuIL-2 therapy.