Menstrual- and gender-dependent variations in circulating IL-1 agonists, antagonists, and binding proteins

This study tested the hypotheses that sex-related differences in circulating binding proteins for interleukin-1β (IL-1β) exist and that these binding proteins affect immunoassays for IL-1β and IL-1Ra. ¹²⁵I- labeled IL-1β was added to human plasma samples, then chromatographed. The percentages of total radioactivity eluting in a high-molecular-weight peak were 21.0 + 0.8 for men (n = 6), 19.1 ± 0.9 for follicular phase women (n = 6), and 18.0 ± 0.8 in luteal phase women (n = 6; men vs. women, P = 0.032; follicular vs. luteal, P = 0.035), and correlated with plasma sIL-1RII concentrations (r = 0.647, P = 0.007). Plasma IL-1β immunoreactivity did not correspond to concurrent cellular secretion rates due, in part, to interference in the IL-1β assay by sIL-1RII. Correspondence between plasma IL-1Ra levels and cellular secretion rates was observed only after serial dilutions of the samples. These results indicate that plasma IL-1β binding capacity differs between men and women and that sIL-1RII is a major contributing factor. Furthermore, relating plasma IL-1 isoform immunoreactivity to functional measures (tracer binding) or concurrent release by isolated cells can lead to insights about assay interferences that may exist in plasma.