P. Fishman et al., PREVENTION OF FETAL LOSS IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME BYINVIVO ADMINISTRATION OF RECOMBINANT INTERLEUKIN-3, The Journal of clinical investigation, 91(4), 1993, pp. 1834-1837
Antiphospholipid antibodies are strongly associated with arterial and
venous thrombosis and with fetal loss. Recently an experimental model
for antiphospholipid syndrome (APLS) was established in our laboratory
. In this model, mice are immunized passively or actively with anticar
diolipin antibodies and acquire the syndrome, which is characterized b
y prolonged activated partial thromboplastin time (APTT), thrombocytop
enia, low fecundity rate, and fetal loss. In a normal process of pregn
ancy, lymphokines affect fetal implantation and development. Cytokines
from the colony stimulating factor family, like GM-CSF and IL-3, were
shown to be positive signals for implantation and to promote placenta
l development and fetal growth. Given our preliminary findings of low
IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal lo
ss in a strain of mice prone to fetal resorption, our aim in the prese
nt study was to examine the effect of murine recombinant IL-3 (mrIL-3)
on pregnant mice induced with experimental APLS. Mice were passively
transfused to the tail vein, 24 h following mating, with anticardiolip
in antibodies. The mice were divided into two groups: one group was in
jected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after
mating, while the control group was injected with PBS. When the mice w
ere killed on day 15 of pregnancy a 32%+/-4.2 resorption rate was obse
rved in the anti-cardiolipin-immunized group, which was reduced to 4%/-0.3 following treatment with mrIL-3. The thrombocytopenia associated
with the experimental APLS was also corrected following lymphokine ad
ministration. IL-3 may be effective in prevention of recurrent fetal l
oss in APLS.