Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Roth, Joachim; Hübschle, Thomas; Pehl, Ulrich; Ross, Günter; Gerstberger, Rüdiger

doi:10.1007/s004240100718

Cited by 48 publications

(28 citation statements)

References 45 publications

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“…Another potential limitation might be a certain heterogeneity between the animals of the 2 series. Since diclofenac induces also dose-dependent fluctuations of systemic cytokine levels, we should point out that the reported effects of diclofenac are also heterogeneous [19,20,21,22]. This was particularly well documented for TNF-α levels where elevation is described after diclofenac treatment but is partially abolished in a dosage of 3 mg/kg body weight s.c. [23].…”

Section: Discussionmentioning

confidence: 95%

Perioperative Diclofenac Application during Video-Assisted Thoracic Surgery Pleurodesis Modulates Early Inflammatory and Fibrinolytic Processes in an Experimental Model

Opitz¹,

Arni²,

Oberreiter³

et al. 2013

Eur Surg Res

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Background/Purpose: It has been substantiated that the quality of pleurodesis is reduced when non-steroidal anti-inflammatory drugs (NSAIDs) are used perioperatively. The effects of NSAID administration on the early inflammatory and fibrinolytic processes after mechanical pleurodesis were investigated in an established pig model. Methods: Left-sided mechanical pleural abrasion was performed on 24 pigs assigned to either an NSAID or a control group. Pleural fluid and blood samples were analysed over a 24-hour period. Histological evaluation of neutrophil influx at the site of pleural abrasion was performed. Results: The volume of pleural effusion was significantly decreased in the diclofenac group at 10 and 24 h, and the protein content was significantly lower. The diclofenac group at 24 h had a diminished total number of white blood cells and a reduced content of transforming growth factor-β. Moreover, the diclofenac group had a reduced percentage of neutrophils at 6 h. Significantly increased levels of D-dimers and tissue plasminogen activator were measured at 6 h and of interleukin-10 at 24 h. Neutrophils at the site of pleural abrasion were significantly reduced. Conclusions: Systemic application of diclofenac led to a local enhancement of fibrinolysis and attenuation of pro-inflammatory and fibrotic processes necessary for adhesion formation in our model.

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Section: Discussionmentioning

confidence: 95%

Perioperative Diclofenac Application during Video-Assisted Thoracic Surgery Pleurodesis Modulates Early Inflammatory and Fibrinolytic Processes in an Experimental Model

Opitz¹,

Arni²,

Oberreiter³

et al. 2013

Eur Surg Res

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“…The increase in CSF PGE 2 probably reflects the induction of COX-2 in the brain capillary endothelial cells where LPS or cytokines transiently enhance COX-2 mRNA and protein levels (31). COX-2 mRNA expression in brain capillary cells is enhanced as early as 1 h after peripheral LPS administration (100 g/kg ip) (6), which is compatible with the development of anorexia and other LPS-induced effects, such as fever and activation of the hypothalamic-pituitary-adrenal axis (35), which are also reported to be mediated by COX-2 and CNS PGs.…”

Section: Discussionmentioning

confidence: 98%

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

Lugarini¹,

Hrupka²,

Schwartz

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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tion attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 g/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE2 levels after LPS administration. LPS induced a time-dependent increase of PGE2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE2, whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE2 as a potential neuromodulator involved in this response.NS-398; resveratrol; prostaglandin E2; food intake; fever LIPOPOLYSACCHARIDE (LPS) and proinflammatory cytokines [e.g., interleukin (IL)-1␤, IL-6, and tumor necrosis factor-␣] induce anorexia and fever (32), two phenomena partly independent of each other. Brain areas involved in feeding and body temperature regulation are activated (5, 40) after peripheral administration of LPS and cytokines. This can be accomplished through neural and/or humoral communications with the central nervous system (CNS). Vagal afferents have been implicated in some of the behavioral effects induced by peripheral LPS or cytokines (3, 16). In our hands, however, subdiaphragmatic vagal deafferentation, alone or in combination with celiac-superior mesenteric ganglionectomy, did not attenuate the anorectic response to peripheral LPS, muramyl dipeptide, and IL-1␤ (33). An alternative route of communication between the periphery and the CNS involves cytokine and LPS receptors on the surface of the cerebral endothelial cells of the brain-blood barrier (1, 39) and subsequent mediators such as prostaglandins (PGs) (6). PGs are synthesized by cyclooxygenase (COX), an enzyme that exists in two different isoforms. COX-1 is constitutively expressed in many tissues, mainly outside the brain, and its levels are relatively insensitive to inflammatory stimulation. COX-1 is scarcely expressed in capillary endothelial and perivascular glial cells (13). COX-2, on the other hand, is constitutively expressed at low levels in neurons of the cortex, hippocampus, and amygdala, but not in the cells of the cerebral vasculature (34). COX-2 is strongly induced in brain vasculature, however, by LPS and IL-1␤ (12,22,34). LPS or cytokines (31) transiently enhance COX-2 mRNA and protein levels via activation of nuclear factor-B (2, 23).In our hands, nonselective pharmacological inhibition of COX by administration of indomethacin or paracetamol attenuated the pyretic and hypophagic effects of peripheral 27). Selective inhibition of COX-2 blocks LPS-induced fever (7). Use of selective inhibitors for COX-1 and -2 could not establ...

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“…Previous studies of the role of COX-1 and COX-2 in LPS fever were done mainly in mice and guinea pigs (Li et al, 1999;Steiner et al, 2001;Roth et al, 2002). However, most work on brain mechanisms of fever were done in rats, and we wanted data comparable to our previous detailed studies of the fever curve and brain Fos responses in i.v.…”

Section: Technical Considerationsmentioning

confidence: 90%

“…COX-1 -/-mice showed typical fevers during the first 2 hours after administration of low dose LPS, but COX-2 -/-mice developed hypothermia (Li et al, 1999). Pretreatment of guinea pigs with a COX-1 inhibitor (SC-560) in a similar model did not affect febrile responses to low doses of LPS, but a COX-2 inhibitor (nimesulide or meloxicam) attenuated the fever (Steiner et al, 2001;Roth et al, 2002). Cao et al (1997) found that a COX-2 inhibitor prevented fever in rats after intraperitoneal LPS, but did not examine the effect of a COX-1 inhibitor.…”

mentioning

confidence: 92%

Specific roles of cyclooxygenase‐1 and cyclooxygenase‐2 in lipopolysaccharide‐induced fever and fos expression in rat brain

Zhang

Lü

Elmquist

et al. 2003

J of Comparative Neurology

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Fever is a coordinated autonomic, endocrine, and behavioral response mediated by the brain in reaction to inflammatory stimuli. An essential step in transmitting the immune signal to the brain is the formation of prostaglandin E2. Cyclooxygenase (COX) is the critical enzyme in the synthesis of prostaglandins and COX-2, the inducible form of the enzyme, is markedly induced in cells associated with the cerebral blood vessels and the leptomeninges by immune stimuli such as intravenous administration of lipopolysaccharide (LPS). However, the specific roles of COX-1, the constitutive form of cyclooxygenase, and COX-2 in LPS-induced fever are not well understood. We injected LPS i.v. in combination with either a highly selective COX-1 (SC-560) or COX-2 (SC-236) inhibitor to determine the effects of each drug on the subsequent fever response and on the pattern of expression of Fos protein in the brain. The COX-2 inhibitor blocked LPS-induced fever and Fos expression in sites such as the ventromedial preoptic nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos-immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and parabrachial nucleus (PB) remained. In contrast, the COX-1 inhibitor resulted in a profound hypothermic response to LPS and blocked LPS-induced Fos-immunoreactivity in the PVH, PB, NTS, and VLM, although it had no effect on the VMPO. Although COX-2 plays a dominant role in mediating fever responses to i.v. LPS, at least some components of the response, including avoiding hypothermia and the induction of Fos in the NTS, VLM, PB, and PVH, appear to depend on COX-1. J.

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Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs

Cited by 48 publications

References 45 publications

Perioperative Diclofenac Application during Video-Assisted Thoracic Surgery Pleurodesis Modulates Early Inflammatory and Fibrinolytic Processes in an Experimental Model

Perioperative Diclofenac Application during Video-Assisted Thoracic Surgery Pleurodesis Modulates Early Inflammatory and Fibrinolytic Processes in an Experimental Model

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

Specific roles of cyclooxygenase‐1 and cyclooxygenase‐2 in lipopolysaccharide‐induced fever and fos expression in rat brain

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