Sex and parity modulate cytokine production during murine ageing.
We have previously shown that physiological hormone differences related to pregnancy or sex affect the age-related distribution of mononuclear cell populations during murine ageing. To determine whether such changes are involved in the age-related changes in functions of T cells, we examined the secretion of major T cell immunoregulatory cytokines (IL-2, IL-4, interferon-gamma (IFN-gamma), IL-3, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) of in vitro concanavalin A-activated spleen cells of C57B1/6 mice. The study included multiparous and virgin females and males at 2, 8, 15 and 23 months of age. Short-term effects of parity (8 months) were evidenced by the decrease of IFN-gamma and the preserved IL-2 production in multiparous females (8 months), while IFN-gamma was unchanged and IL-2 decreased in virgin mice. The increase in IL-4 production appeared earlier in multiparous females (15 months) than in virgin mice (23 months). The increase in IL-4/IFN-gamma and IL-4/IL-2 ratios at 8 and 15 months, respectively, in multiparous females, suggests that pregnancy modifies the Th1/Th2 equilibrium. In late adulthood (15 months), IL-6 and GM-CSF production was higher in multiparous females than in virgin males or females. Sex differences were also noticed: IFN-gamma secretion capacity was lower in males than in females during ageing. This study underlines that the onset, magnitude and kinetics of the age-related changes in cytokine production are parity- and sex-dependent. These changes probably influence the incidence of age-related diseases and may explain the greater longevity of females.
Barrat
F
F
Laboratoire de Pathologie Générale, Microbiologie et Immunologie, Institut National de Recherche Agronomique (INRA), Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort, France.
Lesourd
B
B
Boulouis
H J
HJ
Thibault
D
D
Vincent-Naulleau
S
S
Gjata
B
B
Louise
A
A
Neway
T
T
Pilet
C
C
D000375:Aging / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism*; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012737:Sex Factors; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor