Ongoing immunologic activity after short courses of pulse cyclophosphamide in the NZB/W murine model of systemic lupus erythematosus.
OBJECTIVE
Short courses of intermittent pulse cyclophosphamide (CY) have mitigated ovarian toxicity but have also led to incomplete or unsustained remissions of active systemic lupus erythematosus (SLE) in many patients, prompting an evaluation of the immunologic effects of this regimen in the NZB/W female mouse (B/W) model of human SLE.


METHODS
Phenotypic and functional characteristics of spleen lymphocytes from B/W mice treated with short courses of intraperitoneal (i.p.) CY were compared to those from untreated control B/W mice.


RESULTS
After a single dose (250 mg/kg) of i.p. CY, spleen lymphocyte subpopulations fell abruptly but recovered within 4 weeks. Four monthly doses of i.p. CY (starting at 5 months of age) led to a sustained reduction in spleen lymphocyte subpopulations and a parallel decrease in the number of spleen cells spontaneously secreting immunoglobulin and anti-DNA antibody to about 30% of the number seen in untreated control B/W mice. Lipopolysaccharide induced secretion of total IgG and IgG anti-DNA by cultured spleen cells was not diminished one month after the 4 month course of i.p. CY.


CONCLUSIONS
The 4 month course of i.p. CY produced a marked reduction in the number of activated B cells producing autoantibody, but did not achieve sustained immunomodulation judged by the unaltered proportion of spleen B cells spontaneously secreting immunoglobulin and anti-DNA, as well as the response to polyclonal activators of B cells. These results suggest a continued susceptibility to flares of SLE activity after brief courses of intensive immunosuppressive therapy.
Austin
H A
HA
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA.
Patel
A D
AD
Cadena
C A
CA
Boumpas
D T
DT
Balow
J E
JE
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000917:Antibody Formation; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects; D051379:Mice; D008814:Mice, Inbred NZB / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D003520:Cyclophosphamide