Modulation of body temperature, interleukin-6 and leptin by oral contraceptive use

Objectives: This study examined the hypothesis that oral contraceptives (OC) influence the production of thermo-regulatory cytokines, i.e. interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble glycoprotein 130 (s-gp 130) and leptin, and that OC-induced changes in oral temperature (T _oral) are associated with changes in plasma concentrations of these cytokines. To determine if increases in T _oral are part of a cytokine-driven inflammatory (acute-phase) response, circulating concentrations of the hepatic acute-phase protein C-reactive protein (CRP) were also measured. Methods: Morning T _oral were measured and blood samples were collected from 18 women (19- to 22-years-old) on two occasions: Once during active pill usage (quasi-luteal (QL) phase) and once when no active pills were taken (quasi-follicular (QF) phase). Plasma cytokine and CRP concentrations were measured by immunoassay. Results: T _oral and plasma leptin were higher during QL phase (36.4 ± 0.1°C, 9.3± 1.0 ng/ml) than QF phase (36.1 ± 0.1°C, p<0.01; 7.5± 0.7 ng/ml, p<0.01). Increases in T _oral correlated with increases in plasma leptin (R = 0.55, p = 0.02) and with progestin dose (R = 0.47, p = 0.05) individually as well as with leptin and progestin combined in a multiple regression (R = 0.68, p = 0.01). Plasma IL-6 correlated with progestin dose (R = 0.62, p = 0.006). Although there were no phase-related differences in plasma IL-6, sIL-6R, s-gp130, or CRP, the variation in CRP between individuals correlated with the IL-6 agonist/antagonist ratio combined with progestin dose in a multiple regression (R = 0.71, p = 0.01). Conclusions: These results (a) implicate leptin in basal thermoregulation; (b) indicate that progestins have a significant influence on circulating IL-6 concentrations, and (c) are consistent with the concept that plasma CRP concentrations depend upon combined influences of progestins and bioavailable IL-6.