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The elevation of serum tumor necrosis factor (TNF)‐α and hypothalamic prostaglandin (PG) D2 levels in lipopolysaccharide (LPS)‐induced hypothermia in rats: Possible role of cyclooxygenase (COX)‐1
Author(s) -
Akarsu Eyup S.,
Usanmaz Suzan E.,
Mamuk Soner
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1234.7
Subject(s) - hypothermia , tumor necrosis factor alpha , lipopolysaccharide , cyclooxygenase , endocrinology , prostaglandin e2 , medicine , proinflammatory cytokine , chemistry , prostaglandin , hypothalamus , cytokine , interleukin 6 , inflammation , pharmacology , biochemistry , enzyme
LPS‐induced hypothermia is an adaptive thermoregulatory strategy against immunological challenge in rats. It appears that a selective proinflammatory cytokine (TNF‐α) elevation occurs in the peripheral circulation at the initial phase. Then, an increased PG synthesis may take place in brain, since COX inhibitors abolish the hypothermia. We measured hypothalamic PGD2 and PGE2 levels at this phase. The effects of COX‐1 selective inhibitors (valeryl salicylate [VS] or SC‐560) were also evaluated. LPS ( E. coli O111:B4, 250 μg/kg, ip) produced monophasic hypothermia in biotelemetered adult male Wistar rats. The serum TNF‐α elevation was temporally related with the response. The LPS‐injected rats were sacrificed by microwave irradiation. The 4‐Bromomethyl‐7‐methoxycoumarine derivatives of PGD2 and PGE2 were measured by HPLC in hypothalamic homogenates. The PGD2 increased from 58±5 pg/mg (basal) to 274±18 pg/mg wet tissue weight. The PGE2 levels did not increase. SC‐560 (1 mg/kg, sc) abolished the hypothermia and TNF‐α elevation. But, VS (20 mg/kg, sc) inhibited hypothermia and hypothalamic PGD2 increase, without any effect on serum TNF‐α levels. Data suggest that peripheral induction of TNF‐α may also trigger the PGD2 synthesis in hypothalamus, possibly through COX‐1 dependent mechanisms in LPS‐induced hypothermia in rats. Supported by TUBITAK (SBAG‐AYD‐381) and Ankara University ( )