Effect of age on fever response to recombinant interleukin-6 in a murine model.
BACKGROUND
A blunted or absent fever response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile response to recombinant IL-6 (rIL-6) using a well-defined murine model.


METHODS
Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes.


RESULTS
A dose-response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes.


CONCLUSIONS
Our findings confirm that IL-6 has a role in the pathogenesis of fever and that aging alters the febrile response to rIL-6.
Miller
D J
DJ
Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, West Los Angeles, USA.
Yoshikawa
T T
TT
Norman
D C
DC
D000375:Aging / Q000502:physiology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000175:diagnosis*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D015850:Interleukin-6; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins
D015850:Interleukin-6; D011994:Recombinant Proteins