Peripheral lipopolysaccharide administration induces cytokine mRNA expression in the viscera and brain of fever-refractory mice lacking microsomal prostaglandin E synthase-1.
We examined the expression of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF) alpha in mice lacking microsomal prostaglandin E synthase-1 (mPGES-1), which neither produce prostaglandin E(2), nor mount a febrile response upon immune challenge. Intraperitoneal lipopolysaccharide (LPS) injection resulted in a strongly induced expression of all three cytokines in the brain and viscera, similar to wild-type animals. Several brain regions additionally showed modest induction of receptors for these cytokines in both genotypes. Telemetric recordings of body temperature showed that the mPGES-1 deficient mice remained afebrile upon LPS challenge, in contrast to the prominent fever displayed by the wild-type mice. These data demonstrate that LPS-induced cytokine expression occurs independently of prostaglandin E(2), and imply that endogenously expressed IL-1beta, IL-6, and TNFalpha are not pyrogenic per se, supporting the role of prostaglandin E(2) as the final and obligatory mediator of LPS-induced fever.
Nilsberth
C
C
Linköping University, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping, Sweden. camilla.nilsberth@liu.se
Hamzic
N
N
Norell
M
M
Blomqvist
A
A
D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D005334:Fever / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014781:Viscera / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone