Microsoft Word - NEF117BF

Shouichi Fujimoto, MD, First Department of Internal Medicine, Miyazaki Medical College 5200, Kihara, Kiyotake, Miyazaki 889-16 (Japan) Table 1. Time course change of UProE, UFR and UProE/UCreE following intravenous injection of rIL-2 at a dose of 70 × 104 JRU (mean ± SE, n = 8) Dear Sir, Interleukin-2 (IL-2) is a lymphokine modulating T cell function. Recombinant human IL-2 (rIL-2) has been used in adoptive im-munotherapy for malignancies. The major adverse effect of rIL-2 treatment is the vascular-leak syndrome, in which vascular permeability is increased, resulting in a leakage of proteinaceous fluids [1]. On the other hand, the production of a vascular permeability factor derived from T lymphocytes has been demonstrated in the minimal change ne-phrotic syndrome (MCNS) [2,3]. We reported a patient with nephrotic syndrome, which was considered to occur coincidently with rIL-2 treatment for malignant hemangioepithelio-ma, and where rIL-2 might cause MCNS [4]. In order to clarify whether rIL-2 might be involved in proteinuria associated with a reduction in anionic sites of the glomerular basement membrane (GBM), we studied the acute and chronic effects of rIL-2 in rats. Wistar-Kyoto rats (WKY) were cannulat-ed in the right jugular vein and the bladder, and isotonic saline (20 μl/min) was infused throughout the experiment. Saline or several doses of rIL-2 (Shionogi Pharmaceutical Co., Osaka, Japan) were injected via the jugular vein. Urine samples were collected every 5-10 min. Urine flow rate (UFR), urinary protein excretion (UProE) and urinary creatinine excretion (UCreE) were measured. For the histological study, 0.5% of polyethyleneimine (PEI) was injected as a cationic probe 10 min after the injection of rIL-2 or isotonic saline. UProE did not change after the rIL-2 infusion at doses of 3.5-35 × 104 JRU as compared to the level before injection. However, the injection of rIL-2 at a dose of 70 × 104 JRU caused an increase in UProE by 3-fold in comparison with the control phase and a concomitant increase in UFR by 5-fold. A UProE/UCreE ratio was not different before and after the injection of rIL-2 (table 1). Ten minutes later, these modifications returned to the levels before injection. A dose-dependent increase in UProE was no longer evident in a dose of 140 × 104 JRU of rIL-2. Anionic sites were stained regularly with PEI on the lamina rara externa