PASSIVE DUAL IMMUNIZATION AGAINST TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND IL-1-BETA MAXIMALLY AMELIORATES ACUTE AMINONUCLEOSIDE NEPHROSIS

Rats receiving a single dose (10 mg/100 g) of aminonucleoside of purom ycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted b oth TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first a nd maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo t reatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produ ced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstr ate the effectiveness of immunosuppressive therapy against these two c ytokines in rats with PAN-induced nephrosis.