Lupus nephropathy in New Zealand F1 hybrid mice treated by (-)15-deoxyspergualin

Abstract

The effect of (-)15-deoxyspergualin (15-dsp), a new immunosuppressant which was originally separated from the culture filtrate of a strain of Bacillus laterosporus, was evaluated in this study. Various doses of 15-dsp were subcutaneously administered to New Zealand black/white F1 hybrid mice (B/WF1) four times a week starting at 14 weeks of age, just prior to the onset of nephropathy. The life span of the treated animals, studied at 0.6 to 6.0 mg/kg body weights, compared with the control mice was significantly prolonged by 15-dsp treatment (percent survival of the treated mice at 50 to 70 weeks of age was significantly higher than that of the control mice, except that of the 0.6 mg group at 60 wks of age, P less than 0.05 by Fisher's exact test). In the 6.0 mg group of mice, complete suppression of spontaneously progressive splenomegaly with decreased total spleen cells was observed at 24 through 36 weeks of age compared with the same-aged control group of mice (P less than 0.01). Absolute numbers of L3T4+ splenocytes determined by flow cytometry, as well as L3T4+/Lyt2+ ratio, were decreased, while in vitro interleukin 2 production by splenocytes induced with staphylococcal enterotoxin A was significantly enhanced. Serum IgG anti-ds DNA antibody levels, measured by radioimmunoassay in the treated mice, were significantly lower at 24 through 36 weeks of age than those in the control mice (P less than 0.01), and the incidence of significant proteinuria (greater than or equal to 100 mg/dl) in the 15-dsp group was lower at both 32 and 36 weeks of age (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic effect of 15-deoxyspergualin on the progression of lupus nephritis in MRL mice. I. Immunopathological analyses

“…In a previous paper (Makino et al, 1987b), we showed a suppressive effect of DSP on the development of lupus glomerulonephritis in MRL/Jpr and male BXSB mice. Similar findings were reported in (NZB x NZW)FI mice by others (Okubo et al, 1988). In these studies, the drugs were given at an early stage of disease development.…”

Acteoside, a Component of Stachys Sieboldii MIQ, May Be a Promising Antinephritic Agent (2): Effect of Acteoside on Leukocyte Accumulation in the Glomeruli of Nephritic Rats

“…It has been well demonstrated that cyclosporin A (5, 6), FK506 (7), 15-deoxyspergualin (8,21) and steroids (22,23), which have immunosuppressive action, are effective on a variety of glomerular diseases. Therefore, it is consi dered from this finding that the antinephritic action of these drugs including acteoside may be also mediated by the suppression of the production of various cytokins (24)(25)(26) and down-regulation of adhesion molecules on endothelial cells (27).…”

“…Furthermore, there have been numerous reports that cyclosporin A (5, 6), FK506 (7) and 15-deoxy spergualin (8), immunosuppressive agents, inhibit the progression of glomerular lesions in nephritic rats. These findings suggest that suppression of the activation of the local cell-mediated immune response may be effective on glomerulonephritis.…”

Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action of the immunosuppressive drug mizoribine.

“…In animal models, mizoribine has shown a strong synergistic effect when used in combination with cyclosporine to prolong the survival of canine renal allografts (1)(2)(3)(4)(5), and rat cardiac and partial lung allografts (6). Mizoribine has also been used successfully as a primary immunosuppressive agent in human renal transplantation, with results comparable or supe-(EC 1 .2.1.14), an enzyme required for the synthesis of guanine nucleotides from IMP.…”