Longitudinal evaluation of diagnostics in experimentally infected young calves during subclinical and clinical paratuberculosis.

Five calves were inoculated orally at 2 weeks of age with a dose of 5 × 10(9) colony-forming units of Mycobacterium avium subspecies paratuberculosis (MAP) on 2 consecutive days. Two calves developed clinical Johne's disease at 12 and 16 months of age after being consistently positive for MAP on fecal culture and antibody enzyme-linked immunosorbent assay (ELISA), starting 2 to 3 weeks and 4 to 5 months after inoculation, respectively.

Évaluation longitudinale du diagnostic lors de paratuberculose subclinique et clinique chez de jeunes veaux infectés expérimentalement. Cinq veaux ont été inoculés oralement à l'âge de 2 semaines avec une dose de 5 × 109 unités formatrices de colonies de Mycobacterium avium sous-espèce paratuberculosis (MAP) pendant 2 jours consécutifs. Deux veaux ont développé la maladie de Johne clinique à l'âge de 12 et de 16 mois après avoir obtenu des résultats constamment positifs pour MAP aux cultures de fèces et à l'ELISA, commençant entre 2 et 3 semaines et 4 et 5 mois après l'inoculation, respectivement.(Traduit par Isabelle Vallières).

Immunomodulatory effects of tulathromycin on apoptosis, efferocytosis, and proinflammatory leukotriene B4 production in leukocytes from Actinobacillus pleuropneumoniae-or zymosan-challenged pigs.

OBJECTIVE: To investigate the anti-inflammatory and immunomodulatory properties of tulathromycin in vitro and in experimental models of Actinobacillus pleuropneumoniae-induced pleuropneumonia and zymosan-induced pulmonary inflammation in pigs. ANIMALS: Blood samples from six 8- to 30-week-old healthy male pigs for the in vitro experiment and sixty-five 3-week-old specific pathogen-free pigs. PROCEDURES: Neutrophils and monocyte-derived macrophages were isolated from blood samples. Isolated cells were exposed to tulathromycin (0.02 to 2.0 mg/mL) for various durations and assessed for markers of apoptosis and efferocytosis. For in vivo experiments, pigs were inoculated intratracheally with A pleuropneumoniae, zymosan, or PBS solution (control group) with or without tulathromycin pretreatment (2.5 mg/kg, IM). Bronchoalveolar lavage fluid was collected 3 and 24 hours after inoculation and analyzed for proinflammatory mediators, leukocyte apoptosis, and efferocytosis. RESULTS: In vitro, tulathromycin induced time- and concentration-dependent apoptosis in neutrophils, which enhanced their subsequent clearance by macrophages. In the lungs of both A pleuropneumoniae- and zymosan-challenged pigs, tulathromycin promoted leukocyte apoptosis and efferocytosis and inhibited proinflammatory leukotriene B4 production, with a concurrent reduction in leukocyte necrosis relative to that of control pigs. Tulathromycin also attenuated the degree of lung damage and lesion progression in A pleuropneumoniae-inoculated pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Tulathromycin had immunomodulatory effects in leukocytes in vitro and anti-inflammatory effects in pigs in experimental models of A pleuropneumoniae infection and nonmicrobial-induced pulmonary inflammation. These data suggested that in addition to its antimicrobial properties, tulathromycin may dampen severe proinflammatory responses and drive resolution of inflammation in pigs with microbial pulmonary infections.

Anti-inflammatory effects of retinoids and carotenoid derivatives on caspase-3-dependent apoptosis and efferocytosis of bovine neutrophils.

OBJECTIVE: To evaluate immunomodulatory properties of all-trans retinoic acid and a fully oxidized ß-carotene dietary product in calves with Mannheimia haemolytica-induced pneumonia. ANIMALS: Twenty-five 6- to 10-week-old male Holstein calves for experimental inoculations and three 8- to 30-week-old Angus heifers for blood donations. PROCEDURES: In vitro, neutrophils and monocyte-derived macrophages isolated from blood of healthy Angus heifers were treated with all-trans retinoic acid (1 µM) or fully oxidized ß-carotene (8.3 µg/mL) for various times and assessed for markers of cellular death, antimicrobial function, and production of proinflammatory leukotriene B4. Following 28 days of dietary supplementation with fully oxidized ß-carotene, Holstein calves were experimentally inoculated with M haemolytica. Bronchoalveolar lavage fluid was collected at 3 and 24 hours after challenge inoculation and analyzed for markers of apoptosis. RESULTS: In vitro, all-trans retinoic acid and fully oxidized ß-carotene induced cell-selective, caspase-3-dependent apoptosis in neutrophils, which subsequently enhanced efferocytosis in macrophages. Conversely, neither treatment altered phorbol 12-myristate 13-acetate-induced oxidative burst, phagocytosis of nonopsonized zymosan (complement or antibody independent), or M haemolytica-induced leukotriene B4 production in bovine neutrophils. In vivo, fully oxidized ß-carotene enhanced leukocyte apoptosis in bronchoalveolar lavage fluid as well as subsequent efferocytosis by macrophages without altering numbers of circulating leukocytes. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophil apoptosis and subsequent efferocytosis by macrophages are key mechanisms in the resolution of inflammation. Findings for the present study indicated that all-trans retinoic acid and fully oxidized ß-carotene could be novel nutraceutical strategies that may confer anti-inflammatory benefits for cattle with respiratory tract disease.