Soluble adhesion molecules in serum throughout the menstrual cycle

BACKGROUND: The female reproductive and immune systems are integrally linked with respect to shared cellular and molecular mediators. Cell adhesion molecules (CAMs) involved in leukocyte–endothelial interactions, e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, are regulated by sex steroids when expressed by cultured endothelium, while uterine and ovarian CAM expression appears to be cyclically or gonadotrophin-regulated. METHODS AND RESULTS: To determine if these effects translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels in peripheral blood, normally cycling women received regular venous sampling throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the early and mid-follicular stages, progressively decreased throughout the remainder of the cycle and were significantly reduced in the late luteal stage (P < 0.001). Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration did not vary markedly across the menstrual cycle. Plasma hormone and urinary hormone metabolite levels confirmed precise cycle tracking and revealed an inverse relationship between sICAM-1 and estradiol (r = –0.38, P < 0.005). A negative correlation was also apparent between sVCAM-1 and circulating monocyte cell numbers (r = –0.47, P < 0.001). CONCLUSIONS: The normal cyclic variation in peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or ovarian tissue remodelling events, and is of particular importance if soluble CAM levels are utilized as biological markers of certain disease states in women of reproductive age.