Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

Izui, Shozo; Fernandes, Gabriel; Hara, Ikuo; McConahey, Patricia J.; Jensen, Fred C.; Dixon, Frank J.; Good, Robert A.

doi:10.1084/jem.154.4.1116

Cited by 49 publications

(8 citation statements)

References 34 publications

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“…Calorie-restricted animals lose body weight, and their serum anti-DNA antibodies are significanty decreased [23]. Increases in body weight and antibodies to DNA were unaffected in mice treated with MX-68.…”

Section: Resultsmentioning

confidence: 82%

A Novel Antifolate, MX-68, Inhibits the Development of Autoimmune Disease in MRL/lpr Mice

Mihara¹,

Takagi²,

Urakawa³

et al. 1997

Int Arch Allergy Immunol

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We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.

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Section: Resultsmentioning

confidence: 82%

A Novel Antifolate, MX-68, Inhibits the Development of Autoimmune Disease in MRL/lpr Mice

Mihara¹,

Takagi²,

Urakawa³

et al. 1997

Int Arch Allergy Immunol

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“…Induction of antigen-specific suppressor cells by DSP was suggested by some authors [6], In addition, DSP may at least partially act directly on B cells, since it suppresses plaque-forming cell production against T-independent antigen (TNP Brucella abortus) as well [14]. Lastly, de creased antibody production observed in DSP-treated mice was not due to low caloric intake [15], since their body weight was no different compared with the sameaged control mice.…”

Section: Resultsmentioning

confidence: 96%

Reversal of Established Nephropathy in New Zealand B/W F<sub>1</sub>Mice by 15-Deoxyspergualin

Okubo¹,

Umetani²,

Inoue³

et al. 1991

Nephron

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The therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F₁ mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c, four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt 2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4⁺ cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p < 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32–40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.

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“…Calorie-restricted animals lose body weight, and their serum anti-DNA antibodies are significantly decreased [27]. Gain in body weight was unaffected in mice treated with MR16-1.…”

Section: Discussionmentioning

confidence: 98%

IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice

Mihara¹,

Takagi²,

Takeda³

et al. 1998

Clinical and Experimental Immunology

143

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In the present study, we examined the preventive effect of anti-mouse IL-6 receptor (IL-6R) antibody, MR16-1, on the development of autoimmune kidney disease in female NZB/W F1 (BWF1) mice. Immunological tolerance to MR16-1 or isotype-matched control antibody, KH-5, was induced by the simultaneous administration of anti-CD4 MoAb in mice. Thereafter, mice were intraperitoneally given 0.5 mg of MR16-1, 0.5 mg of KH-5 or saline once a week from 13 to 64 weeks of age. MR16-1 treatment dramatically suppressed proteinuria and prolonged the survival time of BWF1 mice. Only one out of 10 mice died with high levels of proteinuria throughout the experiment. MR16-1 almost completely suppressed the production of IgG forms of anti-DNA and anti-TNP antibodies, but not the IgM forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b and IgG3) of anti-DNA antibody production were significantly suppressed. Moreover, serum IgG1, IgG2a and IgG3 levels in MR16-1-treated mice were lower than those in saline- and KH-5-treated mice, whereas serum IgM and IgA levels were not influenced. In conclusion, MR16-1 potently suppressed the development of autoimmune disease in BWF1 mice, and this was attributed to its effect of specific suppression of IgG class antibody production.

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Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

Cited by 49 publications

References 34 publications

A Novel Antifolate, MX-68, Inhibits the Development of Autoimmune Disease in MRL/lpr Mice

A Novel Antifolate, MX-68, Inhibits the Development of Autoimmune Disease in MRL/lpr Mice

Reversal of Established Nephropathy in New Zealand B/W F<sub>1</sub>Mice by 15-Deoxyspergualin

IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice

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