Evaluating the IL-6 Family of Cytokines Throughout Equine Gestation

Introduction: The interleukin (IL)-6 family of cytokines is grouped by a common receptor subunit (gp130), but functions in distinct but overlapping physiological activities, including regulation of acute phase reaction and the balance between effector and regulatory T cell populations—both of which play a role in successful pregnancy maturation. Methods: Here, we aim to assess the expression profiles of members of the IL-6 cytokine family throughout equine gestation. To do so, RNA Sequencing was performed on chorioallantois and endometrium of mares at 120, 180, 300, and 330 days of gestation (n = 4/stage), as well as 45-day chorioallantois (n = 4) and diestrus endometrium (n = 3). Expression levels of members of the IL-6 cytokine family including ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), galectin-10, oncostatin M (OSM), and IL-6, -11, and -27 were evaluated in addition to the receptors for IL-6 (IL-6R) and the common receptor subunit gp130. Additionally, peripheral concentration of IL-6 was assessed. Results: In the chorioallantois, differential expression of IL-6, IL-11, CNTF, CLCF1, OSM, and CT-1 was noted. In the endometrium, the gestational age of pregnancy impacted the expression of IL-11, CNTF, and CT-1. Circulatory IL-6 concentrations reached their highest concentrations at 120 days, with lesser concentrations noted at 45, 180, 300, and 330 days. Both IL-6R and gp130 altered in expression throughout equine gestation. Conclusion: In conclusion, members of the IL-6 cytokine family appear to fluctuate constantly throughout equine pregnancy, with varying expression profiles noted when comparing individual members. Additionally, different expression profiles were noted when comparing chorioallantois, endometrium, and circulation, indicating that the function of the cytokine is tissue-specific.