Ge. Resch et Wr. Millington, Inhibition of interleukin-l beta and prostaglandin E-2 thermogenesis by glycyl-glutamine, a pro-opiomelanocortin-derived peptide, BRAIN RES, 894(2), 2001, pp. 316-320
Interleukin-1 beta (IL-1 beta) and other cytokines produce fever by stimula
ting prostaglandin E-2 (PGE(2)) synthesis in thermoregulatory regions of th
e preoptic area and anterior hypothalamus (POA/AH). Prostaglandin E-2 is th
ought to raise body temperature, at least in part, by stimulating beta -end
orphin release from pro-opiomelanocortin neurons that innervate the POA/AK.
In this study, we investigated whether glycyl-glutamine (beta -endorphin(3
0-31)), an inhibitory dipeptide synthesized from beta -endorphin post-trans
lationally, inhibits IL-1 beta and PGE(2)-induced hyperthermia. Hyperthermi
c sites were identified by microinjecting PGE(2) (3 fmol/1 mul) into the me
dial preoptic area (mPOA) of conscious, unrestrained rats. Interleukin-1 mu
beta (1 U) injection into the same PGE(2) responsive thermogenic sites in
the mPOA elicited a prolonged rise in colonic temperature (T-c) (+1.02+/-0.
06 degreesC) that persisted for at least 2 h. Glycyl-glutamine (3 nmol) co-
injection into the mPOA inhibited IL-1 beta thermogenesis completely (T-c=-
0.18+/-0.22 degreesC). Glycyl-glutamine had no effect on body temperature w
hen given alone to normothermic rats. Co-injection of individual amino acid
s, glycine and glutamine (3 nmol each amino acid), failed to influence IL-1
beta -induced thermogenesis, which indicates that Gly-Gln hydrolysis does
not explain its inhibitory activity. Glycyl-glutamine (3 nmol) also prevent
ed the rise in body temperature produced by PGE(2) (PGE(2)=0.89+/-0.05 degr
eesC; PGE(2) plus Gly-Gln=-0.16+/-0.14 degreesC), consistent with evidence
that PGE(2) mediates IL-1 beta -induced fever. These findings demonstrate t
hat Gly-Gln inhibits the thermogenic response to endogenous pyrogens. (C) 2
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