Mean ± SEM of clinical characteristics of all dogs on the day of or one day after admission to the clinic.

<p>Mean ± SEM of clinical characteristics of all dogs on the day of or one day after admission to the clinic.</p

Time course of IL-10, TNF-α and 5-LO expression (mean ± SEM) in 24 survivor dogs with acute leptospirosis, including 13 dogs with (group LAPH) and 11 dogs without LAPH (group nLAPH).

<p>Differences between the disease groups LAPH and nLAPH are indicated as <b>+</b> (<i>P</i> < 0.1) and * (<i>P</i> < 0.05). Different letters indicate significant differences between the days (a,b,c for the LAPH group; A,B,C for the nLAPH group). Statistical significance. IL-10: disease effect <i>P</i> = 0.02, time effect <i>P</i><0.01, and interaction <i>P</i> = 0.42; TNF-α: disease effect <i>P</i> = 0.35, time effect <i>P</i><0.01, and interaction <i>P</i> = 0.94; 5-LO: disease effect <i>P</i> = 0.01, time effect <i>P</i> = 0.09, and interaction <i>P</i> = 0.98.</p

Mean ± SEM area under the curve of relative mRNA expression (CT, log₂) of genes encoding cytokines and enzymes in whole blood of diseased dogs during the first three days after admission to the clinic (non-survivors excluded).

<p>Mean ± SEM area under the curve of relative mRNA expression (CT, log₂) of genes encoding cytokines and enzymes in whole blood of diseased dogs during the first three days after admission to the clinic (non-survivors excluded).</p

Detailed primers and conditions used for real-time PCR assays.

<p>Detailed primers and conditions used for real-time PCR assays.</p

Mean ± SEM of mRNA abundance (CT, log₂) of genes encoding cytokines and enzymes in blood of diseased dogs one day before or at the day of death compared to diseased dogs that survived corresponding in time.

<p>Mean ± SEM of mRNA abundance (CT, log₂) of genes encoding cytokines and enzymes in blood of diseased dogs one day before or at the day of death compared to diseased dogs that survived corresponding in time.</p

Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

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. METHODOLOGY AND PRINCIPAL FINDINGS 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. CONCLUSION 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