Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model

Abstract

Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrialtissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rb mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions.

Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model

“…The peritoneal cytokine levels were under detection limit in almost all individuals regarding IL1b, IL-6, IL-2, IFN-c and IL-12. Again, these results in the IL-12 group were consistent with those obtained in the previous observations (Itoh et al 2011). …”

“…In addition, the local administration of IL-2 in the cyst of endometriotic lesions showed suppressive effect of recurrence of endometriosis after GnRH analogues therapy (Acién et al 2003). We have previously reported that not only IL-12 but also IL-2 and IFN-c levels in the peritoneal lavage fluid were not detected on the next day after the final administration of IL-12, even though 0.15 lg/body of IL-12 was intraperitoneally administered for 5 consecutive days (the detection limit was 0.14 pg/mL) (Itoh et al 2011). Therefore, the cytokine levels detected in the peritoneal fluid are thought not to be always parallel to the Il-2 mRNA levels; this could be because the secreted cytokines were immediately removed after interaction with its specific receptor.…”

“…We have recently reported NK cells contribute to suppress development of endometriotic lesions from observations that IL-12 administration for 5 consecutive days, from day -2 through day 2, enhanced cytotoxicity of splenic NK cells at day 3, and that attenuating the cytotoxicity of NK cells by IL-2Rb resulted in an abrogation of suppressive effect of IL-12 (Itoh et al 2011). However, in this study, there was no significant difference in the cytotoxicity of splenic NK cells in all groups (Fig.…”

“…IL-12 is well known to induce Th1 proliferation followed by activation of NK cells by secreting Th1-cell derived cytokines such as IL-2 and interferon-gamma (IFN-c) (Chan et al 1992;Zhou et al 2003). We recently observed suppressive effect of IL-12 on development of ectopic endometriotic lesions and found it was due to activation of natural killer (NK) cells because anti-IL-2 receptor b chain treatment resulted in attenuation of splenic cytotoxicity of NK cells concomitant with suppression of development of endometriotic lesions (Itoh et al 2011).…”

Experimental endometriosis models: different approaches for different tasks

“…В гомологичных моделях иммунная си-стема животных функционирует нормально, поэтому такие модели хорошо подходят для изучения влияния иммуномодулирующих и противовоспалительных препаратов на эндометриоз. Так, в результате лечения ИЛ-12 имплантированных эндометриальных тканей на мышиной модели было высказано предположение, что ИЛ-12 подавляет развитие эндометриоидных оча-гов через активацию NK-клеток [42].…”