Modulation of body temperature, interleukin-6 and leptin by oral contraceptive use.
OBJECTIVE
This study examined the hypothesis that oral contraceptives (OC) influence the production of thermoregulatory cytokines, i.e. interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble glycoprotein 130 (s-gp130) 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 degrees C, 9.3 +/- 1.0 ng/ml) than QF phase (36.1 +/- 0.1 degrees 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.
Salkeld
B D
BD
Noll Physiological Research Center and Department of Kinesiology, Pennsylvania State University, University Park, PA, USA.
MacAulay
J C
JC
Ball
R W
RW
Cannon
J G
JG
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D001831:Body Temperature / Q000187:drug effects / Q000276:immunology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D050822:Cytokine Receptor gp130; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008562:Membrane Glycoproteins / Q000097:blood*; D008597:Menstrual Cycle / Q000187:drug effects* / Q000276:immunology; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000097:blood*; D054411:Receptors, Leptin
D015703:Antigens, CD; D003278:Contraceptives, Oral, Hormonal; C494199:IL6ST protein, human; D015850:Interleukin-6; C515448:LEPR protein, human; D020738:Leptin; D008562:Membrane Glycoproteins; D011372:Progestins; D019947:Receptors, Interleukin-6; D054411:Receptors, Leptin; D050822:Cytokine Receptor gp130; D002097:C-Reactive Protein