[en] ("[en] OBJECTIVE: To evaluate C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) kinetics in dogs with a systemic inflammatory response syndrome (SIRS) presented to an emergency service. We hypothesized serum CRP concentrations would increase and vary during hospitalization, and would correlate with plasma IL-6 and TNF-α concentrations, vary in magnitude according to the underlying disease, and predict survival.
DESIGN: Prospective, observational, clinical study.
SETTING: University emergency department.
ANIMALS: Sixty-nine dogs with SIRS weighing over 5 kg who could tolerate the blood sampling.
INTERVENTIONS: Serum and plasma were collected (and stored at -80°C) at presentation (T0), after 6 (T6), 12 (T12), 24 (T24), and 72 (T72) hours, and at a follow-up visit at least 1 month after discharge (T1m). Underlying diseases were categorized as infection (I), neoplasia (N), trauma (T), gastric-dilation and volvulus (GDV), other gastrointestinal (GI), renal (R), and miscellaneous (M) disease.
MEASUREMENTS AND MAIN RESULTS: Serum CRP concentration was measured using a canine-specific immunoturbidimetric assay. Biologically active plasma IL-6 and TNF-α concentrations were assessed using bioassays. Forty-four dogs survived, 8 died, and 17 were euthanized. Nineteen dogs had follow-up visits. At T0, serum CRP concentration was above the reference interval in 73.1% (49/67), and was within the reference interval (0-141.9 nmol/L) throughout hospitalization in only 6% (4/67). Serum CRP concentrations were significantly higher (P < 0.0001) at T0 (882.9 ± 1082.9 nmol/L) and at all time points during hospitalization (P < 0.0001) compared to T1m, with highest concentrations observed at T24 (906. 7 ± 859.0 nmol/L). At T1m, serum CRP concentrations were within the reference interval (22.9 ± 42.9 nmol/L) in 95% (18/19) of dogs. Logarithmic concentrations of serum CRP and plasma IL-6 were significantly correlated (P < 0.001, r = 0.479). None of the measured cytokines were associated with disease category or outcome.
CONCLUSIONS: Serum CRP concentration is increased in dogs with SIRS, and decreases during treatment and hospitalization. Serum CRP, plasma IL-6, and plasma TNF-α concentrations cannot predict outcome in dogs with SIRS.","[en] ","")
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Gommeren, Kris ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Desmas, Isabelle ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux
Garcia, Alexandra ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés (DCA)
Bauer, Natalie; Department of Veterinary Clinical Sciences, Clinical Pathology, and Clinical Pathophysiology, Justus-Liebig-University Giessen, Giessen, Germany
Moritz, Andreas; Department of Veterinary Clinical Sciences, Clinical Pathology, and Clinical Pathophysiology, Justus-Liebig-University Giessen, Giessen, Germany
Roth, Joachim; Institute for Veterinary Physiology, Justus-Liebig-University Giessen, Giessen, Germany
Peeters, Dominique ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Language :
English
Title :
Inflammatory cytokine and C-reactive protein concentrations in dogs with systemic inflammatory response syndrome.
de Laforcade AM. Systemic inflammatory response syndrome. In: Silverstein DC, Hopper K. eds. Small Animal Critical Care Medicine, 2nd ed. St. Louis, MO: Saunders Elsevier; 2015, pp. 31–34.
Hauptman JG, Walshaw R, Olivier NB. Evaluation of the sensitivity and specificity of diagnostic criteria for sepsis in dogs. Vet Surg 1997; 26:393–397.
Lavrentieva A, Kontakiotis T, Lazaridis L, et al. Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis? Burns 2007; 33:189–194.
Natanson C, Eichenholz PW, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 1989; 169:823–832.
Yu DH, Kim B, Park J. Pathophysiologic and immunologic changes in a canine endotoxemia over a period of 24 hours. J Vet Med Sci 2012; 74:537–544.
Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987; 1:355–357.
Deitschel SJ, Kerl ME, Chang CH, et al. Age-associated changes to pathogen-associated molecular pattern-induced inflammatory mediator production in dogs. J Vet Emerg Crit Care 2010; 20:494–502.
Diebel LN, Liberati DM, Ledgerwood AM, et al. Changes in lymph proteome induced by hemorrhagic shock: the appearance of damage-associated molecular patterns. J Trauma Acute Care Surg 2012; 73:41–50.
Oberholzer A, Souza SM, Tschoeke SK, et al. Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock 2005; 23:488–493.
Pettila V, Hynninen M, Takkunen O, et al. Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis. Intensive Care Med 2002; 28:1220–1225.
Reinhart K, Karzai W, Meisner M. Procalcitonin as a marker of the systemic inflammatory response to infection. Intensive Care Med 2000; 26:1193–1200.
Rau S, Kohn B, Richter C, et al. Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis. Vet Clin Pathol 2007; 36:253–260.
Ceron JJ, Eckersall PD, Martynez-Subiela S. Acute phase proteins in dogs and cats: current knowledge and future perspectives. Vet Clin Pathol 2005; 34:85–99.
Yamashita K, Fujinaga T, Miyamoto T, et al. Canine acute phase response: relationship between serum cytokine activity and acute phase protein in dogs. J Vet Med Sci 1994; 56:487–492.
Murata H, Shimada N, Yoshioka M. Current research on acute phase proteins in veterinary diagnosis: an overview. Vet J 2004; 168:28–40.
Petersen HH, Nielsen JP, Heegaard PM. Application of acute phase protein measurements in veterinary clinical chemistry. Vet Res 2004; 35:163–187.
Ebersole JL, Cappelli D. Acute-phase reactants in infections and inflammatory diseases. Periodontol 2000; 23:19–49.
Yamamoto S, Shida T, Okimura T, et al. Determination of C-reactive protein in serum and plasma from healthy dogs and dogs with pneumonia by ELISA and slide reversed passive latex agglutination test. Vet Q 1994; 16:74–77.
Yamamoto S, Tagata K, Nagahata H, et al. Isolation of canine C-reactive protein and characterization of its properties. Vet Immunol Immunopathol 1992; 30:329–339.
Otabe K, Sugimoto T, Jinbo T, et al. Physiological levels of C-reactive protein in normal canine sera. Vet Res Commun 1998; 22:77–85.
Martinez-Subiela S, Ginel PJ, Ceron JJ. Effects of different glucocorticoid treatments on serum acute phase proteins in dogs. Vet Rec 2004; 154:814–817.
Eckersall PD, Conner JG. Bovine and canine acute phase proteins. Vet Res Commun 1988; 12:169–178.
Eckersall PD, Bell R. Acute phase proteins: biomarkers of infection and inflammation in veterinary medicine. Vet J 2010; 185:23–27.
Tecles F, Spiranelli E, Bonfanti U, et al. Preliminary studies of serum acute-phase protein concentrations in hematologic and neoplastic diseases of the dog. J Vet Intern Med 2005; 19:865–870.
Jergens AE, Schreiner CA, Frank DE, et al. A scoring index for disease activity in canine inflammatory bowel disease. J Vet Intern Med 2003; 17:291–297.
Conner JG, Eckersall PD, Ferguson J, et al. Acute phase response in the dog following surgical trauma. Res Vet Sci 1988; 45:107–110.
Borer LR, Peel JE, Seewald W, et al. Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis. Am J Vet Res 2003; 64:1429–1437.
Martinez-Subiela S, Tecles F, Ceron JJ. Critical differences of acute phase proteins in canine serum samples. Vet J 2003; 166:233–237.
Hayashi S, Jinbo T, Iguchi K, et al. A comparison of the concentrations of C-reactive protein and alpha1-acid glycoprotein in the serum of young and adult dogs with acute inflammation. Vet Res Commun 2001; 25:117–126.
Kuribayashi T, Shimada T, Matsumoto M, et al. Determination of serum C-reactive protein (CRP) in healthy beagle dogs of various ages and pregnant beagle dogs. Exp Anim 2003; 52:387–390.
Kjelgaard-Hansen M, Kristensen AT, Jensen AL. Evaluation of a commercially available enzyme-linked immunosorbent assay (ELISA) for the determination of C-reactive protein in canine serum. J Vet Med A Physiol Pathol Clin Med 2003; 50:164–168.
Ehl S, Gering B, Bartmann P, et al. C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection. Pediatrics 1997; 99:216–221.
Jaswal RS, Kaushal RK, Goel A, et al. Role of C-reactive protein in deciding duration of antibiotic therapy in neonatal septicemia. Indian Pediatr 2003; 40:880–883.
Lowrie M, Penderis J, Eckersall PD, et al. The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs. Vet J 2009; 182:125–130.
Lowrie M, Penderis J, McLaughlin M, et al. Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006–2008). J Vet Intern Med 2009; 23:862–870.
Rikihisa Y, Yamamoto S, Kwak I, et al. C-reactive protein and alpha 1-acid glycoprotein levels in dogs infected with Ehrlichia canis. J Clin Microbiol 1994; 32:912–917.
Martinez-Subiela S, Bernal LJ, Ceron JJ. Serum concentrations of acute-phase proteins in dogs with Leishmaniosis during short-term treatment. Am J Vet Res 2003; 64:1021–1026.
Holm JL, Rozanski EA, Freeman LM, et al. C-reactive protein concentrations in canine acute pancreatitis. J Vet Emerg Crit Care 2004; 14:183–186.
Aziz N, Fahey JL, Detels R, et al. Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood. Clin Diagn Lab Immunol 2003; 10:652–657.
Flower L, Ahuja RH, Humphries SE, et al. Effects of sample handling on the stability of interleukin 6, tumour necrosis factor-alpha and leptin. Cytokine 2000; 12:1712–1716.
Hindenberg S, Klenner-Gastreich S, Kneier N, et al. Evaluation of a species-specific C-reactive protein assay for the dog on the ABX Pentra 400 clinical chemistry analyzer. BMC Vet Res 2017; 13(1):146.
Hillstrom A, Hagman R, Tvedten H, et al. Validation of a commercially available automated canine-specific immunoturbidimetric method for measuring canine C-reactive protein. Vet Clin Pathol 2014; 43:235–243.
Roth J, Martin D, Storr B, et al. Neutralization of pyrogen-induced tumour necrosis factor by its type 1 soluble receptor in guinea-pigs: effects on fever and interleukin-6 release. J Physiol 1998; 509(Pt 1):267–275.
Otto CM, Drobatz KJ, Soter C. Endotoxemia and tumor necrosis factor activity in dogs with naturally occurring parvoviral enteritis. J Vet Intern Med 1997; 11:65–70.
LeMay DR, LeMay LG, Kluger MJ, et al. Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs. Am J Physiol 1990; 259:R126–R132.
Espevik T, Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods 1986; 95:99–105.
Figenschau Y, Sveinbjornsson B, Bertheussen K. Improvement of a cytokine (TNF-alpha) bioassay by serum-free target cell (WEHI 164) cultivation. Cytotechnology 1999; 29:121-134.
Eskandari MK, Nguyen DT, Kunkel SL, et al. WEHI 164 subclone 13 assay for TNF: sensitivity, specificity, and reliability. Immunol Invest 1990; 19:69–79.
Holt I, Cooper RG, Hopkins SJ. Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients. Eur J Clin Invest 1991; 21:479–484.
Aarden LA, De Groot ER, Schaap OL, et al. Production of hybridoma growth factor by human monocytes. Eur J Immunol 1987; 17:1411–1416.
Nordan RP, Richards CD, Gauldie J. Measurement of interleukin 6. Curr Protoc Immunol 2001;Chapter 6:Unit 6 6.
Fransson BA, Lagerstedt A-S, Bergstrom A, et al. C-reactive protein, tumor necrosis factor α, and interleukin-6 in dogs with pyometra and SIRS. J Vet Emerg Crit Care 2007; 17:373–381.
Fransson BA, Karlstam E, Bergstrom A, et al. C-reactive protein in the differentiation of pyometra from cystic endometrial hyperplasia/mucometra in dogs. J Am Anim Hosp Assoc 2004; 40:391–399.
Spapen HD, Hachimi-Idrissi S, Corne L, et al. Diagnostic markers of sepsis in the emergency department. Acta Clin Belg 2006; 61:138–142.
Miyamoto T, Fujinaga T, Yamashita K, et al. Changes of serum cytokine activities and other parameters in dogs with experimentally induced endotoxic shock. Jap J Vet Res 1996; 44:107–118.
Aderka D, Le JM, Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol 1989; 143:3517–3523.
Pullicino EA, Carli F, Poole S, et al. The relationship between the circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response to elective surgery and accidental injury. Lymphokine Res 1990; 9:231–238.
DeClue AE, Sharp CR, Harmon M. Plasma inflammatory mediator concentrations at ICU admission in dogs with naturally developing sepsis. J Vet Intern Med 2012; 26:624–630.
Marks JD, Marks CB, Luce JM, et al. Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration. Am Rev Respir Dis 1990; 141:94–97.
Moscovitz H, Shofer F, Mignott H, et al. Plasma cytokine determinations in emergency department patients as a predictor of bacteremia and infectious disease severity. Crit Care Med 1994; 22:1102–1107.
Yousef AA, Suliman GA. The predictive prognostic values of serum TNF-alpha in comparison to SOFA score monitoring in critically ill patients. Biomed Res Int 2013; 2013:258029.
Falcoz PE, Laluc F, Toubin MM, et al. Usefulness of procalcitonin in the early detection of infection after thoracic surgery. Eur J Cardiothorac Surg 2005; 27:1074–1078.
Bell K, Wattie M, Byth K, et al. Procalcitonin: a marker of bacteraemia in SIRS. Anaesth Intensive Care 2003; 31:629–636.
Sierra R, Rello J, Bailen MA, et al. C-reactive protein used as an early indicator of infection in patients with systemic inflammatory response syndrome. Intensive Care Med 2004; 30:2038–2045.
Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34:1996–2003.
Silvestre J, Povoa P, Coelho L, et al. Is C-reactive protein a good prognostic marker in septic patients? Intensive Care Med 2009; 35:909–913.
Silvestre J, Coelho L, Povoa P. Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 2010; 10:17.
Gebhardt C, Hirschberger J, Rau S, et al. Use of C-reactive protein to predict outcome in dogs with systemic inflammatory response syndrome or sepsis. J Vet Emerg Crit Care 2009; 19:450–458.
Dabrowski R, Kostro K, Lisiecka U, et al. Usefulness of C-reactive protein, serum amyloid A component, and haptoglobin determinations in bitches with pyometra for monitoring early post-ovariohysterectomy complications. Theriogenology 2009; 72:471–476.
Mastrorilli C, Dondi F, Agnoli C, et al. Clinicopathologic features and outcome predictors of Leptospira interrogans Australis serogroup infection in dogs: a retrospective study of 20 cases (2001–2004). J Vet Intern Med 2007; 21:3–10.
Yu DH, Nho DH, Song RH, et al. High-mobility group box 1 as a surrogate prognostic marker in dogs with systemic inflammatory response syndrome. J Vet Emerg Crit Care 2010; 20:298–302.
Oda S, Hirasawa H, Shiga H, et al. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005; 29:169–175.
Martinez-Subiela S, Ceron JJ. Effects of hemolysis, lipemia, hyperbilirrubinemia, and anticoagulants in canine C-reactive protein, serum amyloid A, and ceruloplasmin assays. Can Vet J 2005; 46:625–629.
