Humoral inhibitors of the immune response in uremia. I. Effect of serum and of the supernatant of spleen cultures from uremic rats on the mixed lymphocyte reaction.

The effects of the serum of rats with experimentally induced chronic renal failure and of the supernatant of cultured spleen cells obtained from these animals were tested in the mixed lymphocyte reaction (MLR). Serum of uremic rats with blood urea nitrogen levels greater than 35 mg. per 100 ml. and supernatant of spleen cultures from animals with blood urea nitrogen levels greater than 60 mg. per 100 ml. were found to be inhibitory to the MLR. The inhibitory activity of uremic serum was directly correlated with blood urea nitrogen levels. The inhibitory activities both of uremic serum and of the supernatant of cultured uremic spleen cells were further studied and compared. Dialysis in vitro does not remove the suppressing effect of serum or of supernatant on the MLR. Irreversible inhibition of the MLR is observed after 48 hours' exposure to the serum or to the supernatant; this inhibition occurs whether the MLR culture is exposed during the first 48 hours or last 48 hours of incubation. In some uremic rats the inhibitory activity of the serum disappears or is weakened after splenectomy, despite a continued rise in blood urea nitrogen levels.