Protective role of indomethacin on lipopolysaccharide-stimulated fever induction and cerebral catecholamine biosynthesis in Wistar rat.

OBJECTIVES: The antipyretic and neuroprotective potential of the nonsteroidal anti-inflammatory drug "indomethacin" was tested against lipopolysaccharide-produced hyperthermia and biosynthesis of norepinephrine and dopamine, in six brain regions of male rat.

METHODS: Observations were based on a single intraperitoneal injection of each of lipopolysaccharide (250 µg Kg-1 body wt) and indomethacin (20 mg Kg-1 body wt) followed by sampling and assaying of brain specimens after 2, 8, 12 and 24 hrs. lipopolysaccharide induced a general hyperthermia (8-24 hr) that was completely abolished by pretreatment with indomethacin.

RESULTS: In virtually all brain regions tested, lipopolysaccharide stimulated the biosynthesis of norepinephrine and dopamine. Yet, pretreatment with indomethacin provoked substantial mitigation predominantly after 24 hrs. A time-based manner attended by a regionally nonselective manner characterized lipopolysaccharide-induced monoamine biosynthesis; whereas, indomethacin alleviation seems to proceed in a time-dependent and regionally-selective pathway since the pons proved the fastest and/or most responsive brain region to indomethacin action. A role of prostaglandin synthesis in the development of lipopolysaccharide-induced fever and catecholamine biosynthesis was suggested, given that both responses were abolished by the cyclooxygenase-inhibitor indomethacin.

CONCLUSION: Accordingly, our data verified the potent therapy potential of indomethacin in protecting cerebral noradrenergic and dopaminergic systems against lipopolysaccharide-induced acute phase reactions.