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Cytokines as diagnostic biomarkers in canine pyometra and sepsis

Karlsson, Iulia (2015). Cytokines as diagnostic biomarkers in canine pyometra and sepsis. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2015:46
ISBN 978-91-576-8290-1
eISBN 978-91-576-8291-8
[Doctoral thesis]

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Abstract

Sepsis is a syndrome with high morbidity, mortality and astronomical health care costs and it is challenging to diagnose both in humans and animals due to the lack of suitable diagnostic biomarkers. Although several types of proteins have been suggested as diagnostic biomarkers of sepsis, none of them were shown to be reliable for routine use in the clinical practice. Dogs with uterine bacterial infection called pyometra often develop sepsis and have been suggested as a natural model of sepsis. To investigate whether there is a pattern of biomarkers that can be useful to diagnose bacterial sepsis on early stages in addition to existing clinical criteria, we measured both local gene expression and serum levels of cytokines in dogs with pyometra and compared these levels with known inflammatory markers and blood clotting parameters.

Serum concentrations of keratinocyte-derived chemokine (KC)-like protein and the global clot strength were significantly increased both in dogs with pyometra compared to healthy dogs and in dogs with sepsis compared to dogs without sepsis in pyometra. Moreover, the expression levels of the chemokines interleukin (IL)-8 and C-X-C motif ligand 5 (CXCL5) mRNA were significantly higher in uteri from dogs with pyometra compared to healthy dogs and in cultured stromal endometrial cells derived from uteri of healthy dogs and cocultured with LPS or pathogenic Escherichia coli compared to unstimulated cells. Although serum concentrations of IL-8, high-mobility group box 1 (HMGB1), prostaglandin F2α, IL-2, IL-15, IL-18, interferon (IFN)-γ and monocyte-macrophage colony stimulating factor (MG-CSF) were not different between dogs with or without sepsis in the presence of pyometra, some of these cytokines correlated significantly with clinical parameters such as total white blood cell count (correlated with HMGB1) and KC-like (correlated with IL-8). Measurements of serum IL-10, CXCL10, tumor necrosis factor (TNF)-α, IL-6 and IL-4 will require a more sensitive method in dogs with pyometra.

Our findings suggest that KC-like, CXCL5 and IL-8 may be useful as early diagnostic biomarkers of sepsis in dogs with pyometra. Further investigation of these chemokines in sepsis may help to improve routines in sepsis diagnosis in dogs and possibly also humans.

Authors/Creators:Karlsson, Iulia
Title:Cytokines as diagnostic biomarkers in canine pyometra and sepsis
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :15 April 2015
Depositing date:15 April 2015
Volume:2015:46
Number of Pages:75
Papers/manuscripts:
NumberReferences
IKarlsson I, Hagman R, Johannisson A, Wang L, Karlstam E, Wernersson S (2012). Cytokines as immunological markers for systemic inflammation in dogs with pyometra. Reprod Domest Anim. 2012; 47 Suppl 6:337-41.
IIKarlsson I, Hagman R, Johannisson A, Wang L, Södersten F, Wernersson S. Serum KC-like chemokine concentrations are significantly increased in canine bacterial sepsis (manuscript).
IIIKarlsson I, Hagman R, Guo Y, Humblot P, Wang L, Wernersson S (2015). Pathogenic Escherichia coli and LPS enhance the expression of IL-8, CXCL5 and CXCL10 in canine endometrial stromal cells. Theriogenology (In Press: http://dx.doi.org/10.1016/j.theriogenology.2015.02.008).
IVKarlsson I, Wernersson S, Ambrosen A, Kindahl H, Södersten F, Wang L, Hagman R (2013). Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis. Vet Immunol Immunopathol. 2013;156:64-72.
Place of Publication:Uppsala
Publisher:Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8290-1
ISBN for electronic version:978-91-576-8291-8
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Cell Biology
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Immunology (Immunology in the medical area to be 30110)
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Infectious Medicine
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Clinical Laboratory Medicine
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Agrovoc terms:dogs, sepsis, pyometra, inflammation, cytokines, immune response, indicator organisms, diagnosis
Keywords:sepsis, SIRS, uterine bacterial infection, pyometra, dog, canine, inflammation, cytokines, chemokines
URN:NBN:urn:nbn:se:slu:epsilon-e-2572
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2572
ID Code:12119
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
External funders:Agria and Svenska kennelklubben and Thure F och Karin Forsbergs stiftelse
Deposited By: Iulia Karlsson
Deposited On:16 Apr 2015 11:44
Metadata Last Modified:28 Sep 2015 13:31

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