Lupus nephropathy in New Zealand F1 hybrid mice treated by (-)15-deoxyspergualin.
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)
Okubo
M
M
Department of Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Inoue
K
K
Umetani
N
N
Sato
N
N
Kamata
K
K
Masaki
Y
Y
Uchiyama
T
T
Yan
X J
XJ
Aoyagi
T
T
Shirai
T
T
D000367:Age Factors; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D013154:Spleen / Q000187:drug effects
D006146:Guanidines; D007166:Immunosuppressive Agents; C033797:spergualin; C037258:gusperimus