E. coli 0111:B4 ve 055:B5 serotipi lipopolisakkaritlerinin sıçanlarda oluşturduğu termoregülatuvar ve davranışsal değişikliklerin farmakolojik karakterizasyonu

Abstract

57 SUMMARY In this study, it has been shown that various serotypes of E. coli (0111:B4 and 055:B5) LPSs could induce heterogenous thermoregulatory responses, ie., hypothermia and/or fever in rats. The open field activity and serum TNF-a levels were measured at the initial phases of the hypothermia and fever for characterisation of the E. coli 0111:B4 LPS-induced dual thermoregulatory response. There was no change in the open field activity parameters at the initial phase of both components of dual thermoregulatory response. The TNF-a levels were markedly increased at the initial phase of hypothermia. The effects of various cyclooxygenase (COX) enzyme inhibitors on the dual thermoregulatory response were also evaluated. COX-1 selective inhibitor valeryl salicylate (20, 40, 80 mg/kg) inhibited the hypothermia at all doses tested without an inhibition of increased serum TNF-a levels. Valeryl salicylate did not inhibited fever at any dose. COX-2 selective inhibitor SC- 58236 inhibited the hypothermia partially at lower doses (10, 20 mg/kg), but completely at the highest dose (40 mg/kg) without inhibiting increased serum TNF-a levels. SC-58236 completely abolished the late phase of the fever at all doses tested. DFU, another COX-2 selective inhibitor, found to be ineffective on the dual response at the lowest (1 mg/kg) dose. DFU inhibited the hypothermia completely at higher doses (5, 10 mg/kg). DFU caused an inhibition on the increased serum TNF-a levels at 10 mg/kg dose in which the COX-2 selectivity may have been lost. DFU could only be effective on the fever response when injected two hours after LPS. The combination of valeryl salicylate and SC-58236 caused a complete inhibition of the hypothermic response and the late phase of the fever without affecting the initial phase of the response. Nonselective COX inhibitor diclofenac (3 mg/kg) inhibited the hypothermia partially, but completely abolished the fever response. In conclusion, LPS-induced thermoregulatory responses may be heterogenous and seems to be serotype-specific in rats. Hypothermia could be evaluated as a component of LPS-induced acute phase response, and should have a survival value, like fever. Hypothermia and fever are possibly58 prostaglandin-dependent, centrally-mediated responses. COX-1 isoenzyme may be relatively more important in hypothermia. Besides this, COX-1 isoenzyme does not seem to have a role in fever. COX-2 may be important for the maintenance of fever. Key words: Acute phase response, lipopolysaccharide, fever, hypothermia, telemetry, open field activity, tumor necrosis factor-oc, selective cyclooxygenase inhibitors: valeryl salicylate, SC-58236, DFU, diclofenac, prostaglandins, tromboxane B2, rat.