Effects of Orally Administered Resveratrol on TNF, IL-1ß, Leukocyte Phagocytic Activity and Oxidative Burst Function in Horses: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Study.

Resveratrol, a phytophenol, is a commonly used equine nutraceutical supplement touted to exert anti-inflammatory effects. The effect of orally administered resveratrol on tumor necrosis factor (TNF), interleukin-1ß (IL-1ß), leukocyte phagocytic activity or oxidative burst function have not been reported in horses. The objective of this study was to determine the effects of a commercially available, orally administered resveratrol product on innate immune functions in healthy adult horses. Whole blood was collected from 12 horses prior to and following 3 weeks of treatment with either the manufacturer's recommended dose of resveratrol or placebo. Phagocytosis, oxidative burst and pathogen associated molecular pattern (PAMP) motif-stimulated leukocyte production of TNF and IL-1ß were compared pre- and post-treatment between treatment groups. Phagocytosis and oxidative burst capacity were evaluated via flow cytometry. Tumor necrosis factor and IL-1ß were measured using cytotoxicity and ELISA assays, respectively. There were no significant differences in phagocytosis, oxidative burst or stimulated TNF or IL-1ß production between resveratrol and placebo treatment groups. Orally administered resveratrol at a routinely recommended dose for a duration of 3 weeks did not significantly affect phagocytic activity, oxidative burst function or PAMP-stimulated leukocyte cytokine production.

Immune response to C. novyi-NT immunotherapy.

Clostridium novyi-NT (CVN-NT) spores germinate in hypoxic regions of tumors and have successfully cured induced neoplasia in mouse models and resulted in objective tumor responses in naturally developing neoplasia in the dog. The objective of this pilot, descriptive, prospective, clinical investigation, was to evaluate and describe the immune response to CNV-NT spores to better understand which immune pathways might play a role in the response to this bacteriolytic immunotherapy. Intratumoral injection of CNV-NT spores result in increased phagocytosis and NK cell-like function after treatment. Intravenous injection of CNV-NT spores resulted in increased LPS-induced TNF-α production, LTA-induced IL-10 production and NK cell-like function post-treatment. Increased NK cell-like function was sustained to 28 (intratumoral) or 56 (intravenous) days post-treatment, and increased phagocytic function was sustained to 28 days post-treatment suggesting that CNV-NT spores induce longer-term immune cell function changes. Future investigations evaluating long-term immune system changes and associations between immune function and tumor remission rates should include evaluation of these pathways.

Identification of immunologic and clinical characteristics that predict inflammatory response to C. Novyi-NT bacteriolytic immunotherapy.

BACKGROUND: Clostridium novyi-NT (CNV-NT), has shown promise as a bacterolytic therapy for solid tumors in mouse models and in dogs with naturally developing neoplasia. Factors that impact the immunologic response to therapy are largely unknown. The goal of this pilot study was to determine if plasma immune biomarkers, immune cell function, peripheral blood cytological composition and tumor characteristics including evaluation of a PET imaging surrogate of tumor tissue hypoxia could predict which dogs with naturally developing naïve neoplasia would develop an inflammatory response to CNV-NT. RESULTS: Dogs that developed an inflammatory response to CNV-NT had a higher heart rate, larger gross tumor volume, greater tumor [64Cu]ATSM SUVMax, increased constitutive leukocyte IL-10 production, more robust NK cell-like function and greater peripheral blood lymphocyte counts compared to dogs that did not develop an inflammatory response to CNV-NT. Of these, unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume appeared to be the best predictors of which dogs will develop an inflammatory response to CNV-NT. CONCLUSIONS: Development of inflammation in response to CNV-NT is best predicted by pretreatment unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume.

Defining sepsis in small animals.

OBJECTIVE: To discuss the definitions of sepsis in human and veterinary medicine. DESIGN: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine. SETTING: Veterinary private practice and university teaching hospitals. ANIMALS: Dogs and cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis is a life-threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes. CONCLUSIONS: This review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence-based criteria for its recognition in veterinary clinical practice.

Increasing age and severe intraoperative hypotension associated with nonsurvival in dogs with gallbladder mucocele undergoing cholecystectomy.

OBJECTIVE: To identify prognostic indicators and inflammatory markers associated with nonsurvival in dogs with gallbladder mucoceles (GBMs) following cholecystectomy and to evaluate C-reactive protein (CRP) and haptoglobin concentrations in dogs with GBMs compared to healthy controls. ANIMALS: 25 dogs that underwent cholecystectomy for removal of GBM and 20 healthy control dogs. METHODS: A prospective, multicenter cohort study. Survival outcomes to hospital discharge and 2 weeks postdischarge were recorded from medical records. Laboratory variables, inflammatory markers (CRP and haptoglobin), and 25-hydroxyvitamin(OH) D (25[OH]D) concentrations were measured preoperatively. Associations between signalment, clinicopathologic variables, acute patient physiologic and laboratory evaluation (APPLEFAST) scores, inflammatory markers, 25(OH)D concentration, and survival were analyzed using logistic regression. RESULTS: 76% (19/25) and 68% (17/25) of dogs survived to hospital discharge and 2 weeks postdischarge, respectively. For each additional year of age, the odds of nonsurvival in hospital and 2 weeks postdischarge increased by 2.2 (P = .01; 95% CI, 1.2 to 5.0) and 1.7 (P = .04; 95% CI, 1.0 to 3.2), respectively. Intraoperative systolic blood pressure ≤ 65 mm Hg increased the probability of nonsurvival in hospital (P < .04). Gallbladder perforation, APPLEFAST scores, and preoperative serum concentrations of CRP, haptoglobin, and 25(OH)D were not associated with survival. Serum CRP and haptoglobin concentrations were greater in dogs with GBM compared to controls (P < .001). CLINICAL RELEVANCE: Increasing age and intraoperative systolic blood pressure ≤ 65 mm Hg were associated with nonsurvival in dogs with GBM undergoing cholecystectomy. Serum CRP, haptoglobin, and 25(OH)D were not associated with nonsurvival postcholecystectomy in this sample population.

The tyrosine kinase inhibitor masitinib blunts airway inflammation and improves associated lung mechanics in a feline model of chronic allergic asthma.

BACKGROUND: Blockade of tyrosine kinase signaling by masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, can modulate allergic airway inflammation, but effects on lung mechanics have not been well characterized. We hypothesized masitinib would decrease airway eosinophilia and consequently improve pulmonary mechanics in a feline allergic asthma model. METHODS: Asthma was induced in 12 cats using Bermuda grass allergen (BGA). Cats received 50 mg/day oral masitinib or placebo. Bronchoalveolar lavage fluid (BALF) was analyzed for eosinophils, total protein (TP) and BGA-specific IgE. Ventilator-acquired mechanics after methacholine (MCh) challenge determined MCh concentration needed to increase baseline airway resistance by 200% (EC(200)R(aw)), positive end expiratory occlusion pressure (PEEP) and end inspiratory breath hold pressure (P(plat)). An inverse correlate of respiratory system compliance P(plat)-PEEP was also calculated. Data were analyzed using the Wilcoxon test, with one-tailed significance set at p < 0.1. RESULTS: After 4 weeks, percent eosinophils in BALF was lower in masitinib-treated cats (7 ± 9%) versus controls (30 ± 27%, p = 0.023). BALF TP significantly differed (p = 0.047) between groups, decreasing with masitinib and increasing with placebo. BALF BGA-specific IgE was unaffected by masitinib. Both groups showed an improvement in EC(200)R(aw) (masitinib, p = 0.015; control, p = 0.078) but no significant change in PEEP after 4 weeks. Masitinib-treated cats demonstrated decreased P(plat) (p = 0.033) and P(plat)-PEEP (p = 0.075) at week 4, suggesting an improvement in respiratory compliance. CONCLUSIONS: Masitinib reduced BALF eosinophilia and TP, indicating improved airway inflammation and edema, and improved P(plat) and P(plat)-PEEP, suggesting benefit to respiratory compliance influenced by airway inflammation/edema. Masitinib deserves further study in humans with chronic allergic asthma.

Successful treatment of acute respiratory distress syndrome in 2 dogs.

Acute respiratory distress syndrome (ARDS) was diagnosed in 2 dogs with acute dyspnea. Short-term positive pressure ventilation and intense critical and nursing care were provided. Both dogs improved and were discharged. Few reports describe successful recovery from ARDS. Due to advances in positive pressure ventilation and improvement in the supportive care of critically ill veterinary patients, the prognosis for ARDS may improve.

Clinical and immunologic assessment of sepsis and the systemic inflammatory response syndrome in cats.

OBJECTIVE: To compare clinical findings and inflammatory mediator production among cats with sepsis, cats with noninfectious systemic inflammatory response syndrome (SIRS), and healthy cats. DESIGN: Case-control study. ANIMALS: Cats with sepsis (n = 16) or SIRS (19) and 8 healthy control cats. PROCEDURES: Clinical variables were recorded for each cat, and plasma tumor necrosis factor (TNF) and interleukin (IL)-1ß activities and IL-6 and CXC chemokine ligand (CXCL)-8 concentrations were determined at initial evaluation. RESULTS: Clinicopathologic abnormalities associated with sepsis in cats included a high band neutrophil percentage, eosinopenia, hyponatremia, hypochloremia, hypoalbuminemia, hypocalcemia, and hyperbilirubinemia. When the sepsis and SIRS groups were compared, the only significant differences in the CBC and plasma biochemical findings were band neutrophil percentage and albumin concentration. Cats with sepsis had significantly greater plasma TNF activity than did healthy cats and were more likely to have detectable concentrations of IL-6 than were cats with SIRS or healthy cats. Plasma IL-1ß activity did not differ among groups, and CXCL-8 was not detectable in most (32/43) cats. Mortality rate was not significantly greater for cats with sepsis (7/16) than for cats with SIRS (5/19). Plasma IL-1ß activity and IL-6 and chloride concentrations were the only variables correlated with nonsurvival in the sepsis group. CONCLUSIONS AND CLINICAL RELEVANCE: Cats with sepsis may have various clinicopathologic abnormalities but are more likely to have a high band neutrophil percentage and hypoalbuminemia than cats with noninfectious SIRS. Plasma interleukin-1ß activity and plasma IL-6 and chloride concentrations may be useful prognostic biomarkers for septic cats.

Cortisol and aldosterone response to various doses of cosyntropin in healthy cats.

OBJECTIVE: To determine the lowest dose of cosyntropin on a per body weight basis that would produce maximal cortisol and aldosterone secretion and the ideal timing of blood sample collection after ACTH stimulation in healthy cats. DESIGN: Randomized crossover trial. ANIMALS: 7 adult sexually intact male purpose-bred cats. PROCEDURES: Each cat received saline (0.9% NaCl) solution (control) and 5 doses (125 µg/cat and 10, 5, 2.5, and 1 µg/kg [4.54, 2.27, 1.14, and 0.45 µg/lb]) of cosyntropin IV with a 2-week washout period between treatments. Blood samples were obtained before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after administration of saline solution or cosyntropin. RESULTS: Serum cortisol and aldosterone concentration increased significantly, compared with baseline values, after administration of all cosyntropin doses. Lower doses of cosyntropin resulted in an adrenocortical response equivalent to the traditional dose of 125 µg/cat. The lowest doses of cosyntropin that stimulated a maximal cortisol and aldosterone response were 5 and 2.5 µg/kg, respectively. Lower doses of cosyntropin resulted in a shorter interval between IV administration of cosyntropin and peak serum cortisol and aldosterone concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Low-dose ACTH stimulation testing with IV administration of cosyntropin at 5 µg/kg followed by blood sample collection at 60 to 75 minutes resulted in concurrent peak serum cortisol and aldosterone concentrations that were equivalent to those achieved following administration of cosyntropin at 125 µg/cat, the standard dose currently used.

In vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide-stimulated production of tumor necrosis factor-α, interleukin-6, and interleukin-10 in blood from healthy dogs.

OBJECTIVE: To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in blood from healthy dogs. SAMPLES: Blood samples from 9 healthy dogs. PROCEDURES: Blood samples were incubated with LPS from Escherichia coli O127:B8 or PBSS (control) for 1 hour. Afterward, the samples were incubated with 10µM epinephrine, norepinephrine, or dobutamine or with saline (0.9% NaCl) solution (control) for 23 hours. Leukocyte viability was assessed by use of trypan-blue exclusion in blood from 2 dogs to ensure cell viability was not altered by the catecholamines. Tumor necrosis factor-α, IL-6, and IL-10 concentrations were measured in the supernatant in duplicate with a canine-specific multiplex bead-based assay. Blood samples from 2 dogs were used to create dose-response curves to evaluate whether the observed cytokine modulation was dependent on catecholamine concentration. RESULTS: Incubation of blood with epinephrine and norepinephrine significantly increased LPS-stimulated production of IL-10, compared with the control. Epinephrine and norepinephrine significantly decreased LPS-stimulated production of TNF-α, compared with the control. Epinephrine and norepinephrine did not significantly alter LPS-stimulated production of IL-6. Dobutamine did not alter catecholamine production. CONCLUSIONS AND CLINICAL RELEVANCE: Epinephrine and norepinephrine, but not dobutamine, had immunomodulatory effects on LPS-stimulated TNF-α and IL-10 production in blood from healthy dogs in this in vitro model of sepsis. Data suggested that dobutamine may have immune system-sparing effects in dogs with sepsis.

Correction: Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele.

[This corrects the article DOI: 10.1371/journal.pone.0244102.].

Evaluation of biomarkers in bronchoalveolar lavage fluid for discrimination between asthma and chronic bronchitis in cats.

OBJECTIVE: To compare concentrations of interleukin (IL)-4, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and total nitric oxide (NO) metabolites in bronchoalveolar lavage fluid (BALF) for discrimination between asthma and chronic bronchitis in cats. ANIMALS: 97 cats. PROCEDURES: Cats screened with cytologic examination of BALF included 13 client-owned cats with naturally developing asthma, 8 client-owned cats with chronic bronchitis, 23 research cats with experimentally induced asthma, 33 research cats with experimentally induced nonseptic suppurative inflammation of the airways, and 20 healthy control cats. Banked unconcentrated BALF supernatant samples were assayed for concentrations of IL-4, IFN-gamma, TNF-alpha, and total NO metabolites. RESULTS: Concentrations of IL-4 and IFN-gamma in BALF were less than the limits of detection for most cats, precluding statistical analysis. No significant differences were detected among groups for TNF-alpha concentrations. Concentrations of total NO metabolites were significantly higher in cats with clinical chronic bronchitis, compared with research cats with nonseptic suppurative inflammation or research cats with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: There were no significant differences in tested biomarkers between cats with asthma and healthy control cats. None of the measured cytokines or NO metabolites were useful for discriminating between cats with naturally developing asthma and those with chronic bronchitis.

Transportation and Routine Veterinary Interventions Alter Immune Function in the Dog.

Rapid activation of the hypothalamic pituitary adrenal axis and the sympathetic nervous system are hallmarks of the acute stress response and these systems interact with the immune system by signaling though glucocorticoid and adrenergic receptors on immune cells. There is limited information about the effect of these physiologic responses on immunologic parameters of pet dogs enrolled in clinical studies. The objective of this study was to evaluate how travel, instrumentation, and hospitalization alter immunologic parameters in pet dogs. Blood was collected from healthy dogs in a home environment and from healthy dogs at the time of presentation to the hospital and after instrumentation and 24 hours of hospitalization. We found that lipopolysaccharide (LPS)-induced downregulation of toll like receptor 4 (TLR4) was blunted in dogs exposed to stress. Neutrophil and monocyte major histocompatibility complex class II (MHCII) expression increased after transportation to the veterinary hospital but then became similar to that of the control dogs at the end of hospitalization. Peripheral blood mononuclear cell cytotoxicity function was blunted in dogs exposed to the stress of transportation as well as hospitalization. Neutrophil apoptosis was greater in dogs exposed to stress compared to controls although this effect significantly decreased after hospitalization stress. Conversely, stress did not alter induced or spontaneous cytokine production from leukocytes, neutrophil or monocyte expression of TLR4, LPS-induced downregulation of monocyte TLR4, LPS-induced neutrophil and monocyte expression of MHCII or peripheral blood lymphocyte phenotype. Transportation and instrumentation/hospitalization stress should be considered when interpreting immunologic studies in pet dogs.

Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Gallbladder hypokinesia has been proposed to contribute to its formation and progression. The specific cause of gallbladder stasis in dogs with GBM as well as viable treatment options to resolve dysmotility remains unknown. Vitamin D deficiency is one of the many potential causes of gallbladder hypokinesia in humans and repletion results in complete resolution of stasis. Improving our understanding of the relationship between serum vitamin D and GBM could help identify dogs as a model for humans with gallbladder hypokinesia. Furthermore, this relationship could provide insight into the pathogenesis of GBM and support the need for future studies to investigate vitamin D as a novel treatment target. Therefore, goals of this study were i) to determine if serum 25-hydroxyvitamin(OH)D concentrations were decreased in dogs with GBM, ii) if serum 25(OH)D concentrations were different in clinical versus dogs subclinical for GBM, and iii) to determine if serum 25(OH)D concentrations could predict the ultrasonographic type of GBM. Sixty-two dogs (clinical, n = 26; subclinical, n = 36) with GBM and 20 healthy control dogs were included in this prospective observational study. Serum 25(OH)D concentrations were measured with a competitive chemiluminescence immunoassay. Overall, dogs with GBM had lower serum 25(OH)D concentrations than control dogs (P = 0.004). Subsequent subgroup analysis indicated that this difference was only significant in the subclinical group compared to the control dogs (P = 0.008), and serum 25(OH)D concentrations did not significantly differ between dogs clinical for GBM versus subclinical or control dogs, indicating that inflammatory state in clinical dogs was not the major constituent of the observed findings. Decreasing serum 25(OH)D concentrations, but not clinical status, was associated with a more advanced developmental stage of GBM type determined by ultrasonography. Our results indicate that vitamin D has a role in dogs with GBM. Additional studies are needed to assess if reduced vitamin D in dogs with GBM is a cause or effect of their biliary disease and to investigate if vitamin D supplementation could be beneficial for dogs with GBM.

Prevalence and impact of cholecystitis on outcome in dogs with gallbladder mucocele.

BACKGROUND: Gallbladder mucocele is a potentially life-threatening extrahepatic biliary disease in dogs. The primary aims of this study were to evaluate the prevalence of cholecystitis in dogs with gross and histopathologically confirmed gallbladder mucocele and to investigate if there is an association between cholecystitis, including its subtypes (eg, acute, acute on chronic, with necrosis, chronic), and survival. Our secondary objective was to evaluate if there is an association between cholecystitis and intraoperative bacteriological culture positivity. KEY FINDINGS: Two hundred nineteen dogs with gallbladder mucocele were included in this multi-institutional retrospective study, of which 63 (28.8%) dogs had histopathological evidence of cholecystitis. The most common forms of cholecystitis were acute on chronic (n = 22/63, 34.9%) and with necrosis (n = 20, 31.7%). Thirty-one (14.1%) dogs had growth of at least 1 bacterial isolate; however, 88.7% had antimicrobials administered within the 48 hours before surgery or intraoperatively. There was not an association between cholecystitis or its subtypes and survival. Furthermore, there was not an association between cholecystitis and intraoperative bacteriological culture positivity. A total of 38 (17.4%) dogs either died or were euthanized during hospitalization. SIGNIFICANCE: Cholecystitis is a common comorbidity in dogs with gallbladder mucocele but was not associated with decreased survival.

Enantiomer-specific effects of albuterol on airway inflammation in healthy and asthmatic cats.

BACKGROUND: Racemic (R,S)-albuterol is a 1:1 mixture of an R-enantiomer which has bronchodilatory and anti-inflammatory effects, and an S-enantiomer which is associated with increased airway hyperreactivity and proinflammatory effects. Proinflammatory effects of regularly inhalated and S-albuterol have not been studied in a whole-animal model. We hypothesized that regular administration of R,S-albuterol or S-albuterol, but not R-albuterol, would induce airway inflammation in healthy and asthmatic cats. METHODS: Six healthy and 5 experimentally asthmatic cats were randomized to receive inhaled R,S-albuterol, S-albuterol, R-albuterol, or placebo (saline) twice daily for 2 weeks, followed by a 6-week washout before crossover to the next treatment. Bronchoalveolar lavage fluid was collected for cell counts and cytokine analysis prior to and at the end of each 2-week treatment. RESULTS: Healthy and asthmatic cats receiving R,S- and S-albuterol had higher total lavage cell numbers (p = 0.04 and p = 0.02, respectively) than those receiving R-albuterol and placebo. The number of lavage eosinophils and the TNF-alpha bioactivity was higher in asthmatic cats receiving R,S- and S-albuterol compared with those receiving the other treatments (p = 0.03 and p = 0.004, respectively). In healthy cats, the number of lavage neutrophils was higher when they received R,S- and S-albuterol compared with other treatments (p = 0.04). CONCLUSION: Airway inflammation is induced in both healthy and asthmatic cats with regular inhalation of racemic and S-albuterol, but not with R-albuterol.

feG-COOH blunts eosinophilic airway inflammation in a feline model of allergic asthma.

OBJECTIVE AND DESIGN: This study investigated if feG-COOH would decrease allergen-induced airway inflammation. MATERIALS OR SUBJECTS: Seven adult cats sensitised to Bermuda grass allergen (BGA) to induce an asthmatic phenotype. TREATMENT: Cats were randomized to receive either feG-COOH (1 mg/kg, PO) or placebo (saline 1 ml, PO) immediately prior to BGA aerosol challenge in a cross-over design. METHODS: Bronchoalveolar lavage fluid (BALF) was collected and airway inflammatory response assessed via inflammatory cell number and type; IL-4, IFN-gamma and nitric oxide metabolite concentrations. A paired t test was used to compare parameters with a P < 0.05 considered significant. RESULTS: The BALF eosinophil percentage was significantly lower in asthmatic cats treated with feG compared with placebo (placebo, 35.3 +/- 12.2%; feG, 22.4 +/- 8.6%; P = 0.002). Treatment with feG did not result in a significant change in any other parameter measured. CONCLUSIONS: These data indicate that a single dose of feG-COOH partially attenuates eosinophilic airway inflammation in experimental feline asthma.

Evaluation of subcutaneous versus mucosal (intranasal) allergen-specific rush immunotherapy in experimental feline asthma.

Rush immunotherapy (RIT) is effective for the treatment of experimental feline allergic asthma. In humans, the safety profile of immunotherapy is improved by delivering allergen by a mucosal route. We hypothesized that mucosal (intranasal) RIT would have similar efficacy to subcutaneous RIT with improved safety. Twelve cats sensitized and challenged with Bermuda grass allergen (BGA) were randomized to receive subcutaneous (SC) or intranasal (IN) RIT. Increasing doses of BGA (20-200 microg) were administered over 24h followed by 200 microg BGA weekly as maintenance. Adverse reactions were recorded. Clinical respiratory scores after BGA aerosol challenge, bronchoalveolar lavage fluid (BALF) % eosinophils, and cytokine concentrations were measured before RIT (day 1) and at months 1, 3 and 6 (M1, M3, M6). More adverse events were recorded with SC RIT (n=12) compared with IN RIT (n=6). Respiratory scores were lower by M6 compared with D1 in both the groups. The % BALF eosinophils declined significantly after RIT for both groups (mean+/-SEM, SC RIT D1 62+/-12, M6 9+/-4; IN RIT D1 54+/-9, M6 14+/-6). The BALF IL-4:IFN-gamma ratio significantly decreased over time in the IN RIT group (mean+/-SEM, D1 2.4+/-0.2, M6 1.0+/-0.2). While both protocols decreased eosinophilic airway inflammation, the SC RIT protocol did not cause life-threatening adverse events and demonstrated more consistent resolution of clinical signs after allergen challenge. Either protocol could be considered for the treatment of feline allergic asthma.

Asthma in humans and cats: is there a common sensitivity to aeroallegens in shared environments?

Cats spontaneously develop eosinophilic airway inflammation and airway hyperreactivity that is very similar to human allergic asthma. In addition, household cats share environmental exposures to aeroallergens with humans. We review the scientific literature concerning the pathophysiology of feline asthma, including similarities to human asthma and evidence regarding environmental aeroallergen triggers. Results of pathophysiological studies suggest important similarities between human and feline responses to inhaled allergens. Only a few studies were found that examined the development of disease in cats to environmental aeroallergens. Limited evidence suggests that some environmental allergens can cause disease in both cats and humans. It appears that there is a need for greater communication between human and animal health professionals regarding environmental causes of asthma. Specifically, additional research into linkages between human and feline asthma using both molecular techniques and clinical epidemiological approaches could lead to improved understanding of the environmental risks. Finally, there should be consideration of use of naturally affected and/or experimentally induced (using clinically relevant allergens) asthmatic cats in preclinical trials for novel therapeutic interventions.

Dogs with osteosarcoma have altered pro- and anti-inflammatory cytokine profiles.

BACKGROUND: Current advances in immunotherapy are an exciting area of study in canine osteosarcoma (OSA). The objective of this study was to determine the immune response in dogs with osteosarcoma by measuring stimulated leukocyte production of tumor necrosis factor (TNF), interleukin (IL)-6, IL-10 and TNF and IL-6 to IL-10 ratios. METHODS: Whole blood was collected from dogs with osteosarcoma receiving non-steroidal anti-inflammatory drugs (NSAIDs, n = 11), dogs with osteosarcoma not receiving NSAIDs (n = 14) and healthy dogs (n = 5). RESULTS: No difference in TNF production was found among healthy and OSA dogs regardless of NSAID administration following stimulation with lipopolysaccharide (LPS) (p = .410), lipoteichoic acid (LTA) (p = .693) or PBS (p = .120). Leukocyte IL-6 production was greater in all dogs with OSA after stimulation with LPS (p = .015), LTA (p = .014) and PBS (p = .034) with no difference between OSA dogs receiving NSAIDs and those not. No differences in IL-10 were found among healthy controls and dogs with OSA regardless of NSAID use. There was no difference among groups for LPS-stimulated TNF to IL-10 ratios (p = .407). For LTA-stimulated leukocytes, the TNF to IL-10 ratio was lower in dogs with OSA than in healthy dogs (p = .031) with no difference between OSA NSAID dogs compared to OSA non-NSAID dogs (p = .059). No differences were found in LPS (p = .310)- or LTA (p = .265)-stimulated leukocyte IL-6 to IL-10 production ratios among groups. CONCLUSIONS: Dogs with osteosarcoma have an altered pro- and anti-inflammatory immunologic profile compared to healthy dogs regardless of NSAID use. Further study is indicated to determine the potential prognostic and therapeutic implications of these findings.