title: Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.
abstract: BACKGROUND
  Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form.
  
  
  RESULTS
  The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury.
  
  
  CONCLUSIONS
  The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways.
authors.affiliation: Division of Small Animal Internal Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Maissen-Villiger
authors.affiliation: Division of Small Animal Internal Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Schweighauser
authors.affiliation: Division of Veterinary Physiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: H Anette
authors.initials: HA
authors.lastname: van Dorland
authors.affiliation: Division of Veterinary Physiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Morel
authors.affiliation: Division of Veterinary Physiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Rupert M
authors.initials: RM
authors.lastname: Bruckmaier
authors.affiliation: Division of Experimental Clinical Research, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zurbriggen
authors.affiliation: Division of Small Animal Internal Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty University of Bern, Bern, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Francey
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000662:veterinary*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006470:Hemorrhage / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000662:veterinary*; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007922:Leptospirosis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000662:veterinary*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000662:veterinary*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D015398:Signal Transduction; D016019:Survival Analysis; D013577:Syndrome; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001094:Arachidonate 5-Lipoxygenase; D052247:Nitric Oxide Synthase Type II
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