Response to thyrotropin-releasing hormone (TRH) in a horse with hyperthyroidism associated with a functional thyroid adenoma.

A 16-year-old American Paint Horse gelding was presented for evaluation of weight loss and high serum thyroid hormone concentrations resulting from a functional thyroid adenoma. The horse showed no response to a thyrotropin-releasing hormone (TRH) stimulation test. Clinical signs resolved following surgical removal of the adenoma.

Réponse à l'hormone relâchant la thyrotropine (TRH) chez un cheval avec hyperthyroïdisme associé à un adénome thyroïdien fonctionnel. Un cheval American Paint Horse hongre âgé de 16 ans fut présenté pour évaluation à la suite d'une perte de poids et d'une concentration sérique élevée d'hormone thyroïdienne résultant d'un adénome thyroïdien fonctionnel. Le cheval ne démontrait aucune réponse au test de stimulation de l'hormone relâchant la thyrotropine. Les signes cliniques se sont réglés après le retrait chirurgical de l'adénome.(Traduit par Dr Serge Messier).

Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.

OBJECTIVE: To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. PROCEDURES: Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported the hypothesis that EMS affects horses' inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

OBJECTIVE: To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). ANIMALS: 6 healthy adult mares and 6 horses with EMS. PROCEDURES: Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. RESULTS: Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. CONCLUSIONS AND CLINICAL RELEVANCE: Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

Effects of a "two-hit" model of organ damage on the systemic inflammatory response and development of laminitis in horses.

The role of endotoxemia in the development of laminitis remains unclear. Although systemic inflammation is a risk factor for laminitis in hospitalized horses, experimental endotoxin administration fails to induce the disease. While not sufficient to cause laminitis by itself, endotoxemia might predispose laminar tissue to damage from other mediators during systemic inflammation. In "two-hit" models of organ damage, sequential exposure to inflammatory stimuli primes the immune system and causes exaggerated inflammatory responses during sepsis. Acute laminitis shares many characteristics with sepsis-associated organ failure, therefore an equine "two-hit" sepsis model was employed to test the hypothesis that laminitis develops with increased frequency and severity when repeated inflammatory events exacerbate systemic inflammation and organ damage. Twenty-four light breed mares (10) and geldings (14) with chronic disease conditions or behavioral abnormalities unrelated to laminitis that warranted euthanasia were obtained for the study. Horses were randomly assigned to receive an 8-h intravenous infusion of either lipopolysaccharide (5 ng/kg/h) or saline beginning at -24h, followed by oligofructose (OF; 5 g/kg) via nasogastric tube at 0 h. Euthanasia and tissue collection occurred at Obel grade 2 laminitis, or at 48 h if laminitis had not developed. Liver biopsies were performed at 24h in laminitis non-responders. Blood cytokine gene expression was measured throughout the study period. Lipopolysaccharide and OF administration independently increased mean rectal temperature (P<0.001), heart rate (P=0.003), respiratory rate (P<0.001), and blood interleukin (IL)-1ß gene expression (P<0.0016), but responses to OF were not exaggerated in endotoxin-pretreated horses. The laminitis induction rate did not differ between treatment groups and was 63% overall. When horses were classified as laminitis responders and non-responders, area under the blood IL-1ß expression curve (P=0.010) and liver and lung gene expression of IL-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor-α (P<0.05) were higher in responders following OF administration. The results indicate that endotoxin pretreatment did not enhance responses to OF. However, systemic inflammation was more pronounced in laminitis responders compared to non-responders, and tissue-generated inflammatory mediators could pose a greater risk than those produced by circulating leukocytes.

Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.

OBJECTIVE: To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. ANIMALS: 12 healthy adult horses (10 mares and 2 geldings). PROCEDURES: Horses were randomly assigned to receive LPS (total dose, 80 µg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 µg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed. RESULTS: All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1ß, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1ß expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses. CONCLUSIONS AND CLINICAL RELEVANCE: Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.