Hum. Reprod. Advance Access originally published online on September 21, 2007
Human Reproduction 2007 22(11):3042-3043; doi:10.1093/humrep/dem291
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Letters to the Editor |
Reply: Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
1 Correspondence address. Tel: +81-75-751-3269; Fax: +81-75-761-3967; E-mail: fuji{at}kuhp.kyoto-u.ac.jp
We would like to thank Dr Orvieto for his interest in our study. Based on the findings that hCG directly decreased interleukin (IL)-2 production by human peripheral lymphocyte and mononuclear cells in vitro (Orvieto et al., 2003
), Dr Orvieto speculated that hCG probably causes ovarian hyperstimulation syndrome (OHSS) by stimulating the ovaries to produce and secrete a still unknown intermediate factor which causes the increase in capillary permeability, rather than by directly stimulating the peripheral blood mononuclear cells (PBMCs) to secrete IL-2.
However, as we described in the Introduction section of our paper (Kosaka et al., 2007), we reported that recombinant-hCG (r-hCG) at high concentration stimulates IL-8 production by PBMC (Kosaka et al., 2002). Using anti-hCG antibodies, it was demonstrated that the promotion of IL-8 production by PBMC was specific to r-hCG, and not due to other contaminating factor(s). Importantly, r-hCG stimulated-IL-8 production by PBMC is mediated not through LH/hCG receptor, but through glucose receptor. Therefore, it should be noted that the response of PBMC to hCG might depend on the glycosylation status of hCG reagent(s) (Kosaka et al., 2002).
We also observed that r-hCG-stimulated PBMC effectively promote invasion of murine and human trophoblastic cells by producing bioactive molecules (Egawa et al., 2002; Nakayama et al., 2002), suggesting that hCG affects PBMC function to facilitate embryo implantation (Fujiwara, 2006). In addition, we preliminarily observed that r-hCG promoted vascular endothelial growth factor (VEGF) production by PBMC (unpublished data). Accordingly, taken together with our recent findings (Kosaka et al., 2007), we think it is possible that immune cells produce VEGF and contribute to increased capillary permeability in OHSS.
Very recently, it was reported that r-hCG induced indoleamine 2,3-dioxygenase expression in dendritic cells, which in turn inhibited the activation of diabetogenic CD4(+) and CD8(+) T-cells in mice (Ueno et al., 2007). Therefore, we think that analysis of the direct effects of hCG on immune system should be continued in the future.
References
Egawa H, Fujiwara H, Hirano T, Nakayama T, Higuchi T, Tatsumi K, Mori T, Fujii S. Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells. Hum Reprod (2002) 17:473–480.
Fujiwara H. Immune cells contribute to systemic cross-talk between the embryo and mother during early pregnancy in cooperation with endocrine system. Reprod Med Biol (2006) 5:19–29.[CrossRef]
Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Satoh Y, Egawa H, Higuchi T, Nakayama T, Ueda M, Maeda M, et al. Human chorionic gonadotropin (HCG) activates monocytes to produce IL-8 via a different pathway from luteinizing hormone (LH)/HCG receptor system. J Clin Endocrinol Metab (2002) 87:5199–5208.
Kosaka K, Fujiwara H, Yoshioka S, Fujii S. Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. Hum Reprod (2007) 22:1647–1651.
Nakayama T, Fujiwara H, Maeda M, Inoue T, Yoshioka S, Mori T, Fujii S. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: hCG enhances the effects of PBMC. Hum Reprod (2002) 17:207–212.
Orvieto R, Leites T, Abir R, Bar J, Yoeli R, Feldberg D, Fisch B. Interleukin-2 production in whole blood cell cultures of women undergoing controlled ovarian hyperstimulation for assisted reproductive technology cycles. Am J Reprod Immunol (2003) 50:220–223.[Medline]
Ueno A, Cho S, Cheng L, Wang J, Hou S, Nakano H, Santamaria P, Yang Y. Transient upregulation of indoleamine 2,3-dioxygenase in dendritic cells by human chorionic gonadotropin downregulates autoimmune diabetes. Diabetes (2007) 56:1686–1693.
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