Cyclophosphamide and 15(S)-15 methyl PGE1 correct the T/B lymphocyte ratios of NZB/NZW mice.
The lupus of NZB/NZW F1 female mice is associated with immune complex glomerulonephritis and premature death. Cyclophosphamide and 15(S)-15 methyl PGE1 therapy halt disease progression. Fluorescein conjugated antibodies were utilized to label specific leukocytes and the subsets were quantitated using a Fluorescence Activated Cell Sorter. Normal outbred CD-1 female mice showed a decrease in absolute T and B cell numbers with age, but the ratio of T and B cells remained essentially constant through 9 months of age. By contrast the NZB/W female mice showed decreased numbers of total lymphocytes relative to CD-1 controls at all ages. Moreover relative to CD-1s, there was a far greater decrease in T cell numbers (7 x for NZB/W versus 2 x for CD-1) and B cell numbers failed to decrease with age. The characteristic decline in T lymphocyte numbers and relative increase in B cell numbers in NZB/W mice were corrected with cyclophosphamide and PGE1 therapy. However, there was no selective modification of T cell subsets (L3T4+ or Ly2+) with therapy. Our investigation suggests correction of the abnormal T/B cell ratio may be a useful marker of therapeutic activity in NZB/W mice.
Girard
D
D
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Aloisi
R M
RM
Bliven
M L
ML
Cunningham
A C
AC
Otterness
I G
IG
D000375:Aging; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D007958:Leukocyte Count; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000652:urine; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000652:urine; D013601:T-Lymphocytes / Q000473:pathology*
C025170:15(S)-15-methylprostaglandin E1; D003520:Cyclophosphamide; D000527:Alprostadil