Fever produced by interleukin-11 (IL-11) injected into the anterior hypothalamic pre-optic area of the rat is antagonized by indomethacin.
A number of cytokines including the family of interleukins and the macrophage inflammatory proteins act in the brain to produce fever. The purpose of this study was to determine whether the recently discovered hematopoietic progenitor cell stimulator, interleukin-11 (IL-11), alters the body temperature (Tb) of the rat when the cytokine is delivered directly to the thermosensitive and pyrogen reactive region of the hypothalamus. A guide cannula for micro-injection into the anterior hypothalamic pre-optic area (AH/POA) was implanted stereotaxically in each of 19 male Sprague-Dawley rats. A Mini-mitter transmitter for continuous monitoring of Tb of the animal was implanted i.p. Following postoperative recovery, recombinant human IL-11 was micro-injected in a volume of 1.0 microliter into the AH/POA in a dose of 2.7, 13.5, 27 or 250 ng. rhuIL-11 evoked a dose dependent fever with a mean rise in Tb of 0.91 +/- 0.06 degrees C, 1.68 +/- 0.11 degrees C and 0.99 +/- 0.08 degrees C following 13.5 ng, 27 ng and 250 ng, respectively. No significant change in Tb of the rats was produced by 2.7 ng IL-11 or the CSF control vehicle. A significant decline in the intake of food occurred also after the micro-injection of the 27 ng of IL-11. Prior treatment of the rat with 5.0 mg/kg of a prostaglandin synthesis inhibitor, indomethacin, administered intraperitoneally attenuated significantly the febrile response induced by the 250 ng dose of IL-11. These results demonstrate that IL-11 possesses potent thermogenic properties when acting within the ventral forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
F J
FJ
Lopez-Valpuesta
R D
RD
Myers
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D017370:Interleukin-11 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D011301:Preoptic Area / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D017370:Interleukin-11; D011994:Recombinant Proteins; D007213:Indomethacin