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. 1993 Apr;91(4):1834–1837. doi: 10.1172/JCI116396

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

P Fishman 1, E Falach-Vaknine 1, R Zigelman 1, R Bakimer 1, B Sredni 1, M Djaldetti 1, Y Shoenfeld 1
PMCID: PMC288166  PMID: 8473523

Abstract

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 anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, 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 placental 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 loss in a strain of mice prone to fetal resorption, our aim in the present 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 anticardiolipin antibodies. The mice were divided into two groups: one group was injected 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 were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed 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 administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.

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Selected References

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  1. Alarcón-Segovia D., Sanchez-Guerrero J. Primary antiphospholipid syndrome. J Rheumatol. 1989 Apr;16(4):482–488. [PubMed] [Google Scholar]
  2. Athanassakis I., Bleackley R. C., Paetkau V., Guilbert L., Barr P. J., Wegmann T. G. The immunostimulatory effect of T cells and T cell lymphokines on murine fetally derived placental cells. J Immunol. 1987 Jan 1;138(1):37–44. [PubMed] [Google Scholar]
  3. Bakimer R., Fishman P., Blank M., Sredni B., Djaldetti M., Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest. 1992 May;89(5):1558–1563. doi: 10.1172/JCI115749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blank M., Cohen J., Toder V., Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3069–3073. doi: 10.1073/pnas.88.8.3069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blank M., Krause I., Ben-Bassat M., Shoenfeld Y. Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype. J Autoimmun. 1992 Aug;5(4):495–509. doi: 10.1016/0896-8411(92)90008-e. [DOI] [PubMed] [Google Scholar]
  6. Blasi F., Vassalli J. D., Danø K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol. 1987 Apr;104(4):801–804. doi: 10.1083/jcb.104.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bradley T. R., Stanley E. R., Sumner M. A. Factors from mouse tissues stimulating colony growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1971 Dec;49(6):595–603. doi: 10.1038/icb.1971.65. [DOI] [PubMed] [Google Scholar]
  8. Brown H. L. Antiphospholipid antibodies and recurrent pregnancy loss. Clin Obstet Gynecol. 1991 Mar;34(1):17–26. doi: 10.1097/00003081-199103000-00006. [DOI] [PubMed] [Google Scholar]
  9. Bruno E., Cooper R. J., Briddell R. A., Hoffman R. Further examination of the effects of recombinant cytokines on the proliferation of human megakaryocyte progenitor cells. Blood. 1991 Jun 1;77(11):2339–2346. [PubMed] [Google Scholar]
  10. Cariou R., Tobelem G., Bellucci S., Soria J., Soria C., Maclouf J., Caen J. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation. Thromb Haemost. 1988 Aug 30;60(1):54–58. [PubMed] [Google Scholar]
  11. Chaouat G., Menu E., Clark D. A., Dy M., Minkowski M., Wegmann T. G. Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy. J Reprod Fertil. 1990 Jul;89(2):447–458. doi: 10.1530/jrf.0.0890447. [DOI] [PubMed] [Google Scholar]
  12. Cosgriff T. M., Martin B. A. Low functional and high antigenic antithrombin III level in a patient with the lupus anticoagulant and recurrent thrombosis. Arthritis Rheum. 1981 Jan;24(1):94–96. doi: 10.1002/art.1780240115. [DOI] [PubMed] [Google Scholar]
  13. Debili N., Hegyi E., Navarro S., Katz A., Mouthon M. A., Breton-Gorius J., Vainchenker W. In vitro effects of hematopoietic growth factors on the proliferation, endoreplication, and maturation of human megakaryocytes. Blood. 1991 Jun 1;77(11):2326–2338. [PubMed] [Google Scholar]
  14. Fishman P., Sredni B., Djaldetti M. Recent advances in interleukin-3 research: a review. Isr J Med Sci. 1990 Jul;26(7):414–419. [PubMed] [Google Scholar]
  15. Francis R. B., Jr, McGehee W. G., Feinstein D. I. Endothelial-dependent fibrinolysis in subjects with the lupus anticoagulant and thrombosis. Thromb Haemost. 1988 Jun 16;59(3):412–414. [PubMed] [Google Scholar]
  16. Ganser A., Lindemann A., Seipelt G., Ottmann O. G., Herrmann F., Eder M., Frisch J., Schulz G., Mertelsmann R., Hoelzer D. Effects of recombinant human interleukin-3 in patients with normal hematopoiesis and in patients with bone marrow failure. Blood. 1990 Aug 15;76(4):666–676. [PubMed] [Google Scholar]
  17. Ganser A., Seipelt G., Lindemann A., Ottmann O. G., Falk S., Eder M., Herrmann F., Becher R., Höffken K., Büchner T. Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes. Blood. 1990 Aug 1;76(3):455–462. [PubMed] [Google Scholar]
  18. Hamilton J. A., Vairo G., Knight K. R., Cocks B. G. Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents. Blood. 1991 Feb 1;77(3):616–627. [PubMed] [Google Scholar]
  19. Harris E. N., Gharavi A. E., Hughes G. R. Anti-phospholipid antibodies. Clin Rheum Dis. 1985 Dec;11(3):591–609. [PubMed] [Google Scholar]
  20. Kurzrock R., Talpaz M., Estrov Z., Rosenblum M. G., Gutterman J. U. Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. J Clin Oncol. 1991 Jul;9(7):1241–1250. doi: 10.1200/JCO.1991.9.7.1241. [DOI] [PubMed] [Google Scholar]
  21. Lala P. K., Graham C. H. Mechanisms of trophoblast invasiveness and their control: the role of proteases and protease inhibitors. Cancer Metastasis Rev. 1990 Dec;9(4):369–379. doi: 10.1007/BF00049525. [DOI] [PubMed] [Google Scholar]
  22. Moreb J., Kitchens C. S. Acquired functional protein S deficiency, cerebral venous thrombosis, and coumarin skin necrosis in association with antiphospholipid syndrome: report of two cases. Am J Med. 1989 Aug;87(2):207–210. doi: 10.1016/s0002-9343(89)80698-9. [DOI] [PubMed] [Google Scholar]
  23. Rustin M. H., Bull H. A., Machin S. J., Isenberg D. A., Snaith M. L., Dowd P. M. Effects of the lupus anticoagulant in patients with systemic lupus erythematosus on endothelial cell prostacyclin release and procoagulant activity. J Invest Dermatol. 1988 May;90(5):744–748. doi: 10.1111/1523-1747.ep12560947. [DOI] [PubMed] [Google Scholar]
  24. Sammaritano L. R., Gharavi A. E., Lockshin M. D. Antiphospholipid antibody syndrome: immunologic and clinical aspects. Semin Arthritis Rheum. 1990 Oct;20(2):81–96. doi: 10.1016/0049-0172(90)90021-7. [DOI] [PubMed] [Google Scholar]
  25. Wegmann T. G. The cytokine basis for cross-talk between the maternal immune and reproductive systems. Curr Opin Immunol. 1989;2(5):765–769. doi: 10.1016/0952-7915(90)90048-l. [DOI] [PubMed] [Google Scholar]

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