Cyclophosphamide and 15(S)-15 methyl PGE1 correct the T/B lymphocyte ratios of NZB/NZW mice

Abstract

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.

Effects of dazmegrel, piroxicam and cyclophosphamide on the NZB/W model of SLE

“…Labelled cells were analyzed on a FACS 440 at 400 mW-488 nm wavelength excitation --using a 5 watt argon laser. disease while producing no effects on body weight or the rate of food consumption, It is interesting that in this study cyclophosphamide's protective effects can be related not only to normalization of lymphocyte distribution but also to increased PGE 2 production (thereby producing the positive effects on lupus disease which are seen when exogenous PGE's are administered as a treatment in this model [2,[6][7][8]). Studies in animal models of autoimmune lupus disease indicate that doses of ibuprofen sufficient to suppress TBX 2 generation by 90% in platelets did not result in reduced intrarenal levels of PGE z or TXB 2 and did not alter the development of renal disease or the survival rate of NZB/W or MRL/lpr mice [2,6].…”

“…Cyclophosphamide therapy alone and in combination with corticosteroids and other immunosuppressives is known to prevent lymphoproliferation and the subsequent generation of immune complexes which lead to glomerulonephritis in NZB/ W mice [4,5,8]. The present study confirms cyclophosphamide's ability to prolong survival, inhibit proteinuria and prevent the characteristic changes in the T and B cell subsets of the total lymphocyte population seen in NZB/W autoimmune lupus Figure 3 The effects of cyclophosphamide (A), dazmegreI and piroxicam (B) on changes in the T (Thy1.2) and B (SIG) cell subsets of the total peripheral blood lymphocyte population vs duration of drug exposure in NZB/W mice.…”

“…However, increased rather than decreased renal thromboxane production has been associated with murine lupus disease [2] and with acute endotoxin-induced renal failure in rats [3]. Lastly, immunosuppressive therapy using cyclophosphamide is a known effective treatment of NZB/W murine lupus disease [4,5,8], but whether cyclophosphamide can also produce beneficial results by altering these arachidonate metabolites is not clear.…”