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Abstract

Objective—To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin.

Animals—12 healthy adult horses.

Procedures—Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, and blood samples were analyzed for concentrations of tumor necrosis factor (TNF)-α, interleukin-6, thromboxane B2 (TxB2), 6 keto-prostaglandin F (PGF)1α, total leukocyte count, and PLE concentrations. An ANOVA was used to detect significant differences.

Results—Administration of PLE resulted in significantly lower rectal temperature, heart rate, cardiac output, right atrial pressure, and pulmonary artery pressure and higher total leukocyte counts in treated horses, compared with values for control horses. The TNF-α concentration was significantly less in treated horses than in control horses. The TxB2 and 6 keto- PGF1α concentrations were significantly different between treated and control horses at 30 minutes (TxB2) and at 30 and 60 minutes (6 keto-PGF1α).

Conclusions and Clinical Relevance—Prior infusion of PLE in horses administered a low dose of endotoxin decreased rectal temperature, heart rate, pulmonary artery pressure, and TNF-α concentrations. Results of this study support further evaluation of PLE for use in the treatment of horses with endotoxemia. (Am J Vet Res 2002;63:1370–1378)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess expression and function of cellsurface IgE receptors on the canine mastocytoma cell line C2 maintained in continuous culture.

Sample Population—C2 cells maintained in medium lacking IgE for up to 10 passages before being stored at –80 C.

Procedure—Cells were thawed, cultured in medium without IgE for 1 to 3 passages, sensitized for 7 days with IgE-rich serum from dogs naturally sensitized to Ascaris suum, and stimulated with antigen Asc S1 from A suum, goat polyclonal anti-canine IgE, or calcium ionophore and phorbol myristate acetate (PMA). Percentage of intracellular β-hexosaminidase released and concentration of tumor necrosis factor-α (TNF-α) synthesized after stimulation were determined. Expression of cell-surface IgE receptors was assessed by use of a flow cytometry.

Results—Immunologic stimulation (antigen or anti-IgE) failed to induce release or synthesis of detectable amounts of β-hexosaminidase or TNF-α. In contrast, nonimmunologic stimulation (calcium ionophore and PMA) led to release of β-hexosaminidase (mean ± SEM maximum release, 23.95 ± 1.96%) and synthesis of TNF-α (maximum concentration, 34.34 ± 2.34 pg/106 cells). As revealed by use of flow cytometry, C2 cells expressed surface IgE receptors that bound canine IgE in vitro.

Conclusions and Clinical Relevance—Continuous culture of the canine mastocytoma cell line C2 in medium without exogenous IgE or cytokines and other growth factors resulted in cell-surface expression of nonfunctional IgE receptors. However, C2 cells maintained in continuous culture may still be a useful tool for the evaluation of mast cell responses to nonimmunologic stimulation and IgE receptor differentiation and maturity. (Am J Vet Res 2002;63:763–766)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize cytokine messenger RNA (mRNA) expression in intranasally vaccinated calves after bovine respiratory syncytial virus (BRSV) challenge.

Animals—Twelve 8- to 12-week-old calves.

Procedures—Calves received modified-live BRSV vaccine (vaccinated) or spent tissue culture medium (mock-vaccinated) intranasally, followed by challenge 30 days later with BRSV, or mock challenge with spent tissue culture medium (mock-challenge controls). Interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA was measured in lungs, bronchoalveolar lavage (BAL) fluid cells, pharyngeal tonsils, and tracheobronchial lymph nodes, and tumor necrosis factor-α (TNF-α) mRNA was measured in lungs and BAL fluid cells by reverse transcriptase-competitive polymerase chain reaction assay.

Results—Resistance to clinical signs of disease was conferred in vaccinated calves. Expression of TNF-α mRNA in lungs and BAL fluid cells was higher in mock-vaccinated calves than control or vaccinated calves. In the lung, IL-4 mRNA expression was higher in vaccinated calves than control or mock-vaccinated calves. In pharyngeal tonsils, expression of mRNA for IL-4 and IFN-γ was higher in mock-vaccinated calves than control calves. In tracheobronchial lymph nodes, IFN-γ mRNA expression was higher in mock-vaccinated calves than vaccinated calves.

Conclusions and Clinical Relevance—Although vaccinated calves had decreased clinical signs of disease after BRSV challenge, compared with mock-vaccinated calves, this difference was not related to a T helper type 1 bias, as determined by increased expression of interferon-γ mRNA relative to interleukin-4 mRNA in lungs, BAL fluid cells, or tracheobronchial lymph nodes of vaccinated calves. Pulmonary inflammation was decreased in vaccinated calves as determined by decreased expression of TNF-α mRNA. (Am J Vet Res 2004;65:725–733)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-α (TNF-α) activity in healthy dogs.

Animals—6 healthy adult male dogs.

Procedures—Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-α activity were measured before (day–1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours.

Results—Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-α activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity.

Conclusions and Clinical Relevance—Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 and T3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs. (Am J Vet Res 2003;64:229–234)

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in American Journal of Veterinary Research

Abstract

Objective—To determine plasma endotoxin concentration in horses competing in a 48-, 83-, or 159-km endurance race and its importance with regard to physical, hematologic, or serum and plasma biochemical variables.

Animals—83 horses.

Procedure—Weight and rectal temperature measurements and blood samples were obtained before, during, and after exercise. Blood samples were analyzed for plasma endotoxin concentration; serum antiendotoxin antibody titers; thromboxane B2 (TxB2) and 6- keto-prostaglandin F (PGF) concentrations; tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) activities; WBC, plasma protein, lactate, serum electrolyte, and calcium concentrations; PCV; and creatine kinase activity.

Results—Detection of plasma endotoxin increased during exercise for horses competing at all distances but occurred more frequently in the 48- and 83-km groups. Plasma lactate concentration was significantly greater when endotoxin was concurrently detected. Endotoxin in plasma was not significantly associated with success of race completion. Plasma TxB2 and PGF concentrations and serum IL-6 activity significantly increased with exercise. Horses that had an excellent fitness level (as perceived by their owners) had greater decreases in serum antiendotoxin antibody titers during exercise than did horses perceived as less fit. In horses with better finish times, TxB2 and PGF concentrations were significantly greater and TNFα activity was significantly less than that of slower horses.

Conclusions and Clinical Relevance—Endotoxemia developed during endurance racing, but was significantly correlated with increased plasma lactate concentration and not with other variables indicative of endotoxemia. Plasma TxB2 and PGF concentrations and serum TNFα activity may be associated with performance success. (Am J Vet Res 2003;64:754–761)

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in American Journal of Veterinary Research

Abstract

Objectives

To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-α) in lungs of calves experimentally infected with Pasteurella haemolytica.

Animals

12 weight-ranked Holstein calves.

Procedure

Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 × 108 P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3- hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. Soluble TNF-α and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA.

Results

Treatment with tilmicosin resulted in significant (P< 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-α concentrations were not significantly affected by tilmicosin.

Conclusion

Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function.

Clinical Relevance

By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs. (Am J Vet Res 1998;59:765-771)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate the ability of hyaluronic acid (HA), with and without transforming growth factor β (TGF-β), to stabilize the catabolic processes associated with atrophy of articular cartilage.

Animals

20 adult, skeletally normal, hound-type dogs.

Procedure

Dogs (20 to 30 kg) were randomly assigned to 1 of 5 groups. One group served as untreated controls. Bivalve casts were placed on the left hind limbs of the remaining 16 dogs to limit weightbearing and motion of the limb for 92 days. One group served as the cast control. Beginning on day 56, 3 groups received aseptic intra-articular injections in the left stifles of either 5 mg of HA or 5 mg of HA containing either 20 or 50 μg of TGF-β. Intra-articular injections were repeated at 4-day intervals until the end of the study. On day 92, stifles were harvested at necropsy. Medial femoral condyles were histologically processed, and the articular cartilage was stained for the presence of proteoglycans, stromelysin, tumor necrosis factor (TNF) α, and TNF receptors (p55 and p75).

Results

Decreased metachromasia was evident in the cartilage matrix of all cast groups, with the smallest decrease in the HA-treated group. Stromelysin was immunolocalized in articular cartilage of the cast (left) limbs of cast control and both HA/TGF-β-treated groups. TNF-α was localized in articular cartilage of all cast (left) and right limbs, except those of the HA-treated group. Receptors for TNF were observed in both limbs of untreated control and cast control groups and cast limbs of HA/TGF-β-treated groups. The receptors were not localized in the right limbs of the HA with or without TGF-β-treated groups. TGF-β did not decrease stromelysin or TNF-α or receptors at the doses used.

Conclusions

HA may mediate a chondrostabilizing influence on articular cartilage by down-regulating TNF-α. Importantly, HA appeared to exert its inhibitory influence on TNF-α, as well as stromelysin and TNF receptors, on a systemic basis.

Clinical Relevance

Results provide insight into the mode of action of HA as a therapeutic agent for arthritis and its stabilizing influence on cartilage metabolism. (Am J Vet Res 1996;57:1488-1496)

Free access
in American Journal of Veterinary Research

Abstract

Objectives—To evaluate the role of interleukin (IL)-10 in the inability of monocyte-derived bovine macrophages to kill Mycobacterium avium subsp paratuberculosis organisms in vitro.

Sample Population—Monocytes were obtained from healthy adult Holstein dairy cows that had negative results when tested for infection with M avium subsp paratuberculosis.

Procedure—Monocyte-derived macrophages were incubated with M avium subsp paratuberculosisfor 2, 6, 24, 72, or 96 hours with or without addition of saturating concentrations of a goat anti-human IL-10 that has been documented to neutralize bovine IL-10 activity. Variables assessed included ingestion and killing of M avium subsp paratuberculosis; expression of tumor necrosis factor (TNF)-α, IL-12, IL-8, major histocompatability (MHC) class II, vacuolar H+ ATPase, and B cell CLL/lymphoma 2 (BCL-2); production of nitric oxide; acidification of phagosomes; and apoptosis of macrophages.

Results—Neutralization of IL-10 enabled macrophages to kill 57% of M avium subsp paratuberculosis organisms within 96 hours. It also resulted in an increase in expression of TNF-α, IL-12, IL-8, MHC class II, and vacuolar H+ ATPase; decrease in expression of BCL-2; increase in acidification of phagosomes; apoptosis of macrophages; and production of nitric oxide.

Conclusions and Clinical Relevance—The capacity of M avium subsp paratuberculosis to induce IL-10 expression may be a major determinant of virulence for this organism. (Am J Vet Res 2005;66:721–726)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate lipopolysaccharide (LPS)- induced activation of equine neutrophils in blood.

Sample Population—Blood samples from 5 healthy adult Thoroughbreds.

Procedure—Neutrophil integrin (CD11/CD18) expression, size variation, degranulation, and deformability were measured with and without incubation with LPS. Time and concentration studies were done. The mechanism of endotoxin-induced neutrophil activation was investigated by inactivating complement or preincubating neutrophils with inhibitors of tumor necrosis factor-α (TNF-α) synthesis, prostaglandin-leukotriene synthesis, or plateletactivating factor.

Results—Incubation of equine neutrophils with LPS increased cell surface expression of CD11/CD18, decreased neutrophil deformability, increased and decreased neutrophil size, and induced neutrophil degranulation. The LPS-induced neutrophil activation was attenuated by addition of inhibitors of TNF-α and prostaglandin-leukotriene synthesis.

Conclusion and Clinical Relevance—Equine neutrophils are readily activated in vitro by LPS, resulting in increased expression of integrin adhesion molecules, decreased deformability, variation in neutrophil size, and degranulation. The tests used to detect activated neutrophils in this study may be useful in detecting in vivo neutrophil activation in horses with sepsis and endotoxemia. (Am J Vet Res 2002;63:811–815)

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in American Journal of Veterinary Research

transcription factor A, mitochondrial. 14 These DAMPs are highly inflammatory and, among other effects, cause upregulation of TNFα in splenocytes, production of type I interferons by plasmacytoid dendritic cells, and marked neutrophil chemotaxis in mice and

Full access
in American Journal of Veterinary Research