TY - JOUR
T1 - Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats
AU - Agus, D.
AU - Mann, R.
AU - Cohn, D.
AU - Michaud, L.
AU - Kelly, C.
AU - Clayman, M.
AU - Neilson, E. G.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1985
Y1 - 1985
N2 - The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (αTBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1±0.2 vs. LP = 1.1±0.3;P<0.001), and serum creatinine values were concordantly different (NP = 1.34±0.02 vs. LP = 0.82±0.03). Titers of αTBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established αTBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0≠0.2; creatinine = 1.78≠0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2±0.3 vs. LP = 1.4±0.2; P<0.001), and serum creatinine values were concordantly different (NP = 1.92±0.05 vs. LP = 0.97±0.02). Again, the titers of αTBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.
AB - The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (αTBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1±0.2 vs. LP = 1.1±0.3;P<0.001), and serum creatinine values were concordantly different (NP = 1.34±0.02 vs. LP = 0.82±0.03). Titers of αTBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established αTBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0≠0.2; creatinine = 1.78≠0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2±0.3 vs. LP = 1.4±0.2; P<0.001), and serum creatinine values were concordantly different (NP = 1.92±0.05 vs. LP = 0.97±0.02). Again, the titers of αTBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.
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U2 - 10.1172/JCI112092
DO - 10.1172/JCI112092
M3 - Article
C2 - 4044836
AN - SCOPUS:0022353718
VL - 76
SP - 930
EP - 936
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -