Role of Prostaglandin E2 and Indomethacin in the Febrile Response of Pigeons

Abstract

Birds, like mammals, develop a febrile response after an injection of bacterial endotoxin [1][2][3][4][5][6][7][8][9] or following bacterial infection [10,11]. In most mammals, prostaglandin E 2 (PGE 2 ) has been found to be an important mediator of fever [12,13], though some studies of avian fever concluded that the central mechanism causing the febrile rise of core temperature (T core ) in birds differs from that in mammals. Although it has been described that the inhibitors of prostaglandin synthesis such as INDO or aspirin lower the febrile response in chickens [1,5] and pigeons [10], these findings cannot be generalized. Artunkal et al. found that the pyretic effect of intrahypothalamic injections of PGE 1 in chickens was intensified and prolonged after a blockade of prostaglandin synthesis with INDO [14]. Recently, Fraifeld et al. reported that systemic injection LPS elicited fever in chicken, but without an elevation of hypothalamic PGE 2 production [15]. Because of these conflicting results, the aim of the present study was to investigate the role of PGE 2 and INDO in fever generation in pigeons. MATERIALS AND METHODSThis study was approved by the Committee of Animal Care of Tokyo Metropolitan Institute of Gerontology. Twenty-four domestic pigeons (Columba livia) weighing 474.6Ϯ44.3 g (meanϮSD) were used in this study. Japanese Journal of Physiology, 53, 253-258, 2003 Key words: lipopolysaccharide, fever, indomethacin, prostaglandin E 2 , pigeon.Abstract: Intravenous (I.V.) injection of 10 g/ kg Escherichia coli lipopolysaccharide (LPS), applied at 13:00, evoked in pigeons a biphasic rise of core temperature (T core ), so that LPS induced with a latency of 30 min first a decrease of T core , and 90 min after LPS, T core increased, obtaining maximum values from 18:00 to 20:00.Prostaglandins have been considered to be importantly involved in fevers in mammals. To investigate an involvement of prostaglandins in the cyclic variations of T core in birds, pigeons were injected I.V. with either 10 mg/kg indomethacin (INDO) or 100 mg/kg aspirin, or they were treated with intracerebroventricular (I.C.V.) injections of 100 g/kg INDO at various times before or after LPS. When INDO or aspirin was I.V. injected 30 or 15 min before LPS, it diminished the initial decrease of T core by more than 50%, whereas the I.V. injection of these drugs 2 and 4 h after LPS did not affect the febrile rise of T core . I.C.V. injections of INDO given either before or after LPS neither influenced the initial drop of T core nor the following febrile hyperthermia. Both the I.V. injection of 1 mg/kg prostaglandin E 2 (PGE 2 ) and the I.C.V. injection of 1 g/kg PGE 2 lowered T core . Our observations suggest that prostaglandins are not involved in the febrile elevation of T core in pigeons, but appear to participate in the decrease of T core , which shortly follows the I.V. injection of LPS. This initial drop of T core following LPS may be caused by a peripheral action of prostaglandins because it was not influenced by the I.C.V. inje...

The development of endotoxin tolerance, and the role of hypothalamo-pituitary-adrenal function and glucocorticoids in Pekin ducks

“…It is likely that other bird species would develop tolerance in the same way that our ducks became hypo-responsive to endotoxin because: (1) the febrile mechanism is thought to be evolutionary conserved (Ewald, 1980); (2) the response of ducks, chickens, pigeons and sparrows to LPS is comparable (Adelman et al, 2010;Johnson et al, 1993a;Maloney and Gray, 1998;Nomoto, 1996);and (3) there is evidence that the physiological mechanism, underlying fever in Pekin ducks, is common to other avian orders (Gray et al, 2005;Johnson et al, 1993b;Nomoto, 2003). There are also similarities in the function of the innate immune response in birds and in mammals; for instance, there is evidence that the activation of the innate immune response via a family of toll-like receptors and the ensuing release of pro-inflammatory cytokines are equivalent in both phyla (Gray et al, 2005;Romanovsky et al, 2005).…”

“…Birds and mammals develop fever when injected with bacterial endotoxin, lipopolysaccharide (LPS) from the cell walls of gramnegative bacteria (Blatteis et al, 2000;Cartmell and Mitchell, 2005;D'Alecy and Kluger, 1975;Gray et al, 2005;Macari et al, 1993;Maloney and Gray, 1998;Nomoto, 2003;Romanovsky et al, 2005). In mammals, repeated exposure to LPS within 1 to 10 days results in a reduction and, in some instances, the total abolition of the febrile response to the same stimulus (Kawasaki et al, 1987;Roth et al, 1997;Roth et al, 1994).…”

Brain IL-6- and PG-dependent actions of IL-1β and lipopolysaccharide in avian fever

“…Furthermore, indomethacin had no effect on the rising phase of fever in pigeons (10 mg/kg iv or 100 g/kg icv) (32), whereas another PG synthesis inhibitor, diclofenac (5 and 15 mg/kg ip), reduced LPS-induced fevers in Pekin ducks (14). Fraifeld et al (13) did not detect an increase in PGE 2 in the brain tissue of febrile chickens, and Nomoto (32) reported that, in pigeons, LPS seems to stimulate PG synthesis at peripheral sites only. It is clear that a contribution of PG to avian fever requires clarification, because PGs are known to regulate many physiological functions in birds, including circulation and respiration, which are closely related to thermoregulation (21,48).…”

“…The PG synthesis inhibitor indomethacin abolished LPS-induced fever in broilers (10 mg/kg iv) (23) but only reduced the duration of fever in young chicks (50 mg/kg iv) (2). Furthermore, indomethacin had no effect on the rising phase of fever in pigeons (10 mg/kg iv or 100 g/kg icv) (32), whereas another PG synthesis inhibitor, diclofenac (5 and 15 mg/kg ip), reduced LPS-induced fevers in Pekin ducks (14). Fraifeld et al (13) did not detect an increase in PGE 2 in the brain tissue of febrile chickens, and Nomoto (32) reported that, in pigeons, LPS seems to stimulate PG synthesis at peripheral sites only.…”

“…With regard to PGs, intracerebroventricular injection of PGE 1 and PGE 2 induced fever in fowls and broilers (23,30,31) and young chicks (1,2) at thermoneutrality, but intracerebroventricular injection of PGF 2␣ and PGE 2 decreased the body temperature (T b ) of fowls and pigeons, respectively (31,32). The PG synthesis inhibitor indomethacin abolished LPS-induced fever in broilers (10 mg/kg iv) (23) but only reduced the duration of fever in young chicks (50 mg/kg iv) (2).…”