relationships among acute phase response proteins, cytokines, and enzymes during ovine experimental endotoxemia

The acute phase response is beneficial to the animal in restoring homeostasis, and measuring the circulating acute phase proteins, cytokines, and enzymes can be used to evaluate the innate immune system's responses to invader agents such as bacterial lipopolysaccharide. Measurement of these parameters has shown to be useful as diagnostic and prognostic markers in animal endotoxemia. The aim of the present experimental study was expression of the acute phase response following the induction of endotoxemia by Escherichia coli serotype O55:B5 in sheep and the relationships among the acute phase response parameters during endotoxemia and their changing patterns. Five clinically healthy 1-year-old Iranian fattailed ewes [25 +/- 1.5 kg, bodyweight] were randomly selected and lipopolysaccharide from Escherichia coli serotype O55:B5 was infused at 20 micro g/kg intravenously to each animal. Fluid therapy was performed in all ewes over 120 minutes after lipopolysaccharide injection and continued for 180 minutes. Blood samples were collected from all ewes prior and 1, 2, 3, 4, 5, 6, and 24 hours after lipopolysaccharide injection and sera were separated. Serum concentrations of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferon-gamma, superoxide dismutase, and glutathione peroxidase were assayed. The rapid and significant elevation of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, and interferon-gamma were seen after endotoxemia induction. Serum concentrations of superoxide dismutase and glutathione peroxidase were significantly decreased after intravenous lipopolysaccharide infusion. The results of the present experimental study showed that haptoglobin, serum amyloid A, tumor necrosis factor-alpha, and interferon-gamma at all hours studied after endotoxemia induction were positively correlated together. These parameters were negatively correlated with superoxide dismutase and glutathione peroxidase at all hours after lipopolysaccharide infusion. The results of the present experiment can provide evidence for associations among acute phase proteins, cytokines, and enzymes and their changes during endotoxemia in sheep

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; percentGR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 æg/mouse, N = 8) and TNF-alpha (2 æg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 æg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 æg/mouse, N = 11), but not antibody neutralization of TNF-alpha (200 æg/mouse, N = 11), reversed the increase of GR ( percentGR 78.8 ± 3.3 vs 47.2 ± 7.5 percent) and the delay of GIT (geometric center 3.7 ± 0.4 vs 5.6 ± 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-alpha neutralization (N = 9) reversed the increase of GR ( percentGR 33.7 ± 2.0 vs 19.1 ± 2.6 percent (1400 W) and 20.1 ± 2.0 percent (anti-TNF-alpha)), but only TNF-alpha neutralization reversed the delay of GIT (geometric center 3.9 ± 0.4 vs 5.9 ± 0.2). These findings suggest that iNOS, but not TNF-alpha, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-alpha is associated with delayed GIT.

Bloqueio do óxido nítrico com L-name compromete a microcirculaçäo hepática durante endotoxinemia / Blockade of NO with L-NAME jeopardize hepatic microcirculation during endotoxemia

O bloqueio da produção do óxido nítrico durante endotoxinemia permanece controvertido. Visando avaliar o efeito do bloqueio do óxido nítrico na microcirculação hepática, ratos Sprague-Dawley machos receberam LPS e depois de 2h foram tratados com L-NAME (10 mg/kg, n=6) ou solução salina (NS, n=7). A perfusão sinusoidal foi avaliada pela microscopia intravital, sangue foi colhido das veias hepáticas para determinação do equilíbrio ácido-básico, e a bile produzida durante todo o experimento foi mensurada. Depois de 1h de tratamento L-NAME acentuou a falência da perfusão sinusoidal induzida pelo LPS (p<0.05 vs NS), acentuando a acidose no sangue efluente hepático (p<0.05 vs NS), enquanto o fluxo biliar apresentou uma redução adicional (L-NAME 2.0 + ou - 0.5 vs NS 2.4 + ou - 0.1 (l/g/min). O bloqueio não-seletivo do óxido nítrico na endotoxinemia aumenta a falência da perfusão sinusoidal, piora o equilíbrio ácido-básico do fígado e tende a acentuar a deficiência da função excretora.