Systemic Inflammation In Dogs Research Articles

Association of leukergy (in vitro leukocyte aggregation) with systemic inflammation in dogs and cats (2017-2022).

Leukergy is the phenomenon of aggregation of leukocytes on a peripheral blood film, and in humans, it is used as an indicator of systemic inflammation and infection. To assess the association of leukergy on blood film examination with biochemical and clinical evidence of systemic inflammation, infection, neoplasia, or specific organ system disease. A case-control study using retrospective analysis (2017-2022) identified all canine and feline patients that had been presented to an academic referral center with a finding of leukergy on peripheral blood film and an equal number of species-matched controls. A total of 127 cases (canine n = 44, feline n = 83) were identified, as well as 127 controls. Feline samples were 7.6× more likely to exhibit leukergy (0.019%) than canine (0.0025%). A positive association was noted between leukergy and higher globulin concentrations in dogs (marginal difference 0.5 mg/dL, P = .016) and cats (marginal difference 0.67 mg/dL, P = <.001). Cats with leukergy had higher WBC counts and were less likely to be diagnosed with cardiac or urinary tract disease than controls. Dogs with leukergy had lower WBC counts and were more likely to be febrile but were less likely to have urinary tract disease than controls. No association was found with neutrophil toxic change or band forms, systemic antimicrobial therapy, or signalment. We conclude that there is a positive association between increased globulin concentrations and leukergy and inconsistent associations between leukergy and other markers of inflammation or infection. Leukergy is rare overall but markedly more common in cats than dogs.

C-reactive protein as a tool for monitoring response to treatment in dogs with acute hemorrhagic diarrhea syndrome.

C-reactive protein (CRP) is an established marker for systemic inflammation in dogs that is especially elevated in dogs with sepsis. Some dogs with acute hemorrhagic diarrhea syndrome (AHDS) develop bacterial translocation and consequent sepsis during hospitalization. This study aimed to evaluate the course of CRP plasma concentrations during hospitalization and its correlation with clinical and other laboratory variables in dogs with AHDS. In this prospective, observational study, CRP was evaluated on days 0, 1, 2, and 3 in 27 client-owned dogs who presented with AHDS. Clinical examination data, blood pressure, acute patient physiologic and laboratory evaluation (APPLE) full and APPLE fast scores, and canine hemorrhagic diarrhea severity (CHDS) index were measured on the same days to evaluate the severity of the disease. Twenty-five of the 27 dogs were discharged from hospital. Nineteen dogs received antimicrobial treatment due to sepsis or neutropenia. CRP values were mildly elevated on day 0 (median 27.3 mg/L; 1.0-125.8 mg/L) and markedly elevated on day 1 (median 88.9 mg/L; 1.4-192.7 mg/L). CRP concentrations decreased gradually over the following days. Moreover, CRP concentrations correlated moderately with albumin, leucocyte count, neutrophil count, and APPLE full and fast scores, but not with antimicrobial treatment. CRP concentrations were significantly elevated in patients with AHDS. In this study population, CRP did not help in detecting the requirement of antimicrobial treatment in dogs with AHDS. Nevertheless, as CRP can monitor the response to treatment, regular analysis can guide treatment.

Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis.

BackgroundAcute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion.ObjectivesExamine PIs and inflammatory mediator concentrations in dogs with AP and their association with death.AnimalsThirty‐one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs.MethodsAntithrombin and α2‐antiplasmin activity (ATA and α2AP, respectively) and concentrations of α1‐proteinase inhibitor (α1PI), α2‐macroglobulin (α2MG), C‐reactive protein (CRP), interleukins (ILs)‐2,6,8 and tumor necrosis factor‐α (TNF‐α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems.ResultsMortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL‐6, and TNF‐α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL‐2, IL‐8, α1PI, and α2AP concentrations did not differ between groups. Serum α2MG concentration was not reliably detected. Serum cPLI, CRP, and IL‐6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL‐6 concentrations.Conclusions and Clinical ImportanceSystemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2AP and α1PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.

Effects of Ovariohysterectomy and Hyperbaric Oxygen Therapy on Systemic Inflammation and Oxidation in Dogs.

Introduction: Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen in a specialized compression chamber leading to hyperoxia. This treatment modality is associated with anti-inflammatory, antioxidant, and healing properties in people and laboratory animals. However, there are relatively few reports that evaluate the effects of HBOT in companion animals. The goal of this study was to investigate the physiological effects of HBOT on surgically induced systemic inflammation and oxidation in dogs.Material and Methods: Twelve healthy female beagle dogs were spayed and randomized into control and HBOT groups (n = 6). Both groups received conventional post-ovariohysterectomy therapy, and the HBOT group received two hyperbaric treatments at 2.0 atmosphere of absolute pressure and 100% oxygen for 35 min, 6 and 18 h after surgery. Blood samples were collected 3 h prior to ovariohysterectomy, 6, 18, and 30 h after surgery, prior to HBOT when applicable. Inflammatory biomarkers, including C-reactive protein, circulating cytokines, and changes in iron homeostasis were evaluated at each time point to determine the effects of surgery and HBOT on inflammation. Similarly, serum total oxidant status and total antioxidant status were measured to assess the oxidative stress. Pain and incision scores were recorded and compared between groups.Results: Following ovariohysterectomy, all dogs had significantly increased serum concentrations of C-reactive protein, KC-like, IL-6, and increased unsaturated iron-binding capacity compared to their pre-surgical values (p < 0.02), while serum iron, total iron-binding capacity and transferrin saturation were significantly decreased after surgery (p < 0.02). There was no significant difference between the control group and the HBOT group for any of the variables. There were no overt adverse effects in the HBOT group.Conclusion: This is the first prospective randomized controlled study to investigate the effects of HBOT on surgically induced systemic inflammation in dogs. While elective ovariohysterectomy resulted in mild inflammation, the described HBOT protocol portrayed no outward adverse effect and did not induce any detectable pro-inflammatory, anti-inflammatory, or antioxidant effects. Additional investigation is required to identify objective markers to quantify the response to HBOT and determine its role as an adjunctive therapy in dogs with more severe, complicated or chronic diseases.

Systemic inflammation in dogs with advanced-stage heart failure

BackgroundAlthough human studies have shown that inflammation plays a role in the development of congestive heart failure, scarce information exists on white blood cell count (WBC) and differential cell counts in various stages of heart failure in man and dogs. A few studies demonstrated increased concentrations of C-reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs. Our research aimed to investigate whether CRP concentration, WBC and neutrophil count (NEUT), as markers of systemic inflammation, are elevated in canine cardiovascular patients. We also aimed to find out whether there is an association between CRP concentration and WBC and NEUT, as well as associations between these inflammatory markers and selected echocardiographic parameters. Sixty-two client-owned canine cardiac patients and 12 healthy dogs were included in the study. The patients were classified into International Small Animal Cardiac Health Council classes (ISACHC I–III). The serum CRP concentration was determined using a canine CRP test kit. WBC and NEUT were determined using an automated hematology analyzer.ResultsSignificantly higher serum CRP concentration, WBC and NEUT were found in the decompensated stage of heart failure (ISACHC III) compared with healthy dogs and with patients in ISACHC group II and ISACHC group I. Serum CRP concentration significantly positively correlated with WBC (r = 0.65, P < 0.001) and NEUT (r = 0.58, P = 0.002) in the ISACHC III group, while no significant correlations were found in the ISACHC I and II groups. A significant negative correlation between serum CRP concentration and the left ventricular ejection fraction (r = − 0.49, P = 0.046) and a significant positive correlation between CRP and the E wave velocity of the mitral valve inflow (r = 0.52, P = 0.046) were found in the ISACHC III group.ConclusionsThe CRP concentration, WBC and NEUT were significantly increased in advanced-stage heart failure patients in comparison with compensated patients and healthy dogs, which indicate the presence of systemic inflammation. However, normal CRP concentration and normal WBC and NEUT can also be present in heart failure.

C-reactive protein: quantitative marker of surgical trauma and post-surgical complications in dogs: a systematic review.

C-reactive protein (CRP) is a major acute phase protein showing increasing serum concentrations in dogs with systemic inflammation following e.g., surgery, trauma, infections, or neoplasia. CRP is a useful diagnostic marker of systemic inflammation in dogs and automated assays have been validated for reliable measurements for routine diagnostic purposes. In the present study available evidence for the use of CRP as a marker of surgery related systemic inflammation in dogs was reviewed and assessed. Two main themes were in focus: (1) canine CRP as a potential marker of postsurgical infectious complications and (2) canine CRP as a marker of the degree of surgical trauma. As outlined in the review several studies suggest that CRP is a useful marker for both purposes. However, the evidence level is limited and studies in the field are all affected by considerable risks of bias. Thus, further studies are needed in order to confirm the assumptions from previous studies and increase the level of evidence for CRP as a useful marker for detecting inflammation after surgery in dogs.

Plasma iron, C-reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome.

To investigate the diagnostic and prognostic value over time of plasma iron compared with the inflammatory markers albumin, C-reactive protein (CRP), and fibrinogen in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational study of sequentially enrolled dogs. ICU of a veterinary teaching hospital. One hundred and sixteen client-owned dogs: 54 dogs with SIRS or sepsis, 42 with focal inflammation, and 20 clinically healthy dogs. Blood samples were obtained on admission in all study groups, and then on alternate days until discharge or death in both inflammation groups. On admission, dogs with SIRS had significantly lower plasma iron (65 ± 5.8 μg/dL, P = 0.001) concentrations than dogs with focal inflammation (89.5 ± 6.2 μg/dL, P = 0.001). Plasma iron, albumin, and CRP effectively discriminated the SIRS/sepsis group from those presenting with focal inflammation with areas under the curve for the receiver operating curves of 0.679, 0.834, and 0.704, respectively. The admission values for these variables did not discriminate survivors from nonsurvivors within the SIRS/sepsis group. However, the magnitude of increase in iron concentration and the decrease in CRP concentration from admission to hospital discharge was higher in survivors than in nonsurvivors within the SIRS/septic group (22.8 vs. 2.51 μg/dL, respectively, P = 0.021 for iron; -67.1 vs. -4.1 mg/L, respectively, P = 0.002 for CRP), resulting in iron and CRP concentrations at hospital discharge for survivors similar to those in the focal inflammation group. Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes.

Increased concentrations of Serum amyloid A in dogs with sepsis caused by pyometra.

BackgroundSepsis is a serious and potentially life-threatening condition and early diagnosis and appropriate treatment is crucial for survival. Pyometra is one of the most common diseases in intact female dogs. The disease often leads to sepsis (systemic inflammatory response syndrome, SIRS, caused by infection). Diagnostic markers for detecting sepsis are gaining increasing interest in veterinary medicine. Acute phase proteins (APPs) such as C-reactive protein (CRP) are useful for detecting systemic inflammation in dogs. Serum amyloid A (SAA) is another major APP in dogs that is not yet as widely used. Albumin is regarded as a negative APP and has earlier been evaluated for prediction of prognosis in septic dogs. The aim of the present study was to determine SAA, CRP and albumin concentrations in dogs with sepsis and pyometra and to evaluate whether these inflammatory markers are associated with length of postoperative hospitalization.ResultsThirty-one surgically treated bitches with pyometra were included, whereof 23 septic (SIRS-positive) and eight non-septic (SIRS-negative). Albumin concentrations were analyzed by routine automated methods. SAA and CRP analyses were performed with previously validated commercially available assays (ELISA and immunoturbidimetric).Mean (±SE) serum concentrations of SAA were significantly higher in septic (130.8 ± 8.0 mg/L) compared to non-septic bitches (88.5 ± 12.5 mg/L). Using a cut-off value for SAA of 109.07 mg/L (n = 31 bitches), the sensitivity and specificity for detecting sepsis was 74% and 50%, respectively. Serum albumin concentrations were not significantly different in septic compared to non-septic bitches (mean ± SE, 25 ± 1 g/L and 26 ± 1 g/L, respectively). CRP concentrations were also not significantly different in septic (mean ± SE 225.6 ± 16.0 mg/L) compared to non-septic bitches (mean ± SE, 176.0 ± 27.1 mg/L). None of these inflammatory markers were associated with the outcome as measured by length of hospitalization.ConclusionsSAA concentrations were increased in dogs with sepsis induced by pyometra and may be useful as an adjunctive diagnostic marker for sepsis. To evaluate the full potential of SAA as a marker for sepsis also in other diseases, further studies are warranted.

Canine serum C‐reactive protein as a quantitative marker of the inflammatory stimulus of aseptic elective soft tissue surgery

C-reactive protein (CRP) is an established serum marker for the presence of systemic inflammation in dogs. Results from previous experimental and clinical studies suggest that CRP concentrations also quantitatively reflect the degree and progress of an inflammatory process, suggesting its use for inflammation monitoring. The objective was to investigate whether the canine CRP response in serum correlates with the amount of trauma and the consequent inflammatory response after 3 standard aseptic soft-tissue surgical procedures in 3 groups of dogs. A total of 24 client-owned intact female dogs of various breeds were enrolled in a clinical study with random allocation into 2 surgical groups, for either conventional, open-approach ovariohysterectomy (OVH; n = 14) or laparoscopic assisted OVH (n = 10). In addition, a group of 8 male Beagles from a laboratory animal facility underwent vasectomy, serving as the third and mildest surgical trauma group. Serum CRP was measured pre- and at 4, 8, 12, 23, and 27 hours postsurgery. Cumulative concentration over time and point concentrations of CRP were correlated with the surgical trauma impact level. There was a significant surgery trauma-related difference in cumulative CRP concentrations among the 3 groups, and also in the 12 hours postsurgery concentration. The CRP response varied according to the degree of surgical trauma on 3 standardized levels, thus supporting the use of canine serum concentrations of CRP as an inflammatory activity indicator and monitoring marker.

Canine Serum Amyloid A (SAA) Measured by Automated Latex Agglutination Turbidimetry Is Useful for Routine Sensitive and Specific Detection of Systemic Inflammation in a General Clinical Setting

Canine serum amyloid A (SAA) is a useful diagnostic marker of systemic inflammation. A latex agglutination turbidimetric immunoassay (LAT) was validated for automated measurements. The aim of the study was to evaluate the clinical applicability of SAA measured by the LAT. SAA was measured in 7 groups of dogs with and without systemic inflammation (n=247). Overlap performance was investigated. Diagnostic performance was compared to body temperature and leukocyte markers. Clinical decision limits for SAA were estimated. In dogs with neurological, neoplastic or gastrointestinal disorders (n=143), it was investigated whether a higher proportion of SAA positive dogs could be detected in cases of complications with risk of systemic inflammation. Significantly higher concentrations of SAA were measured in dogs with (range [48.75; 5,032 mg/l]), compared to dogs without systemic inflammation [0; 56.4 mg/l]. SAA was a more sensitive and specific marker of systemic inflammation (area under the receiver-operating characteristic curve (AUC) 1.00), compared to body temperature (0.6) and segmented neutrophils (best performing leukocyte marker, 0.84). A clinical decision limit of 56.4 mg/l was established giving close to perfect discrimination between dogs with and without systemic inflammation. Higher proportions of SAA-positive dogs were observed in dogs with neurological, neoplastic and gastrointestinal disorders with complications known to increase risk of systemic inflammation, compared to uncomplicated cases. The automated LAT makes SAA applicable as a relevant diagnostic marker of systemic inflammation in dogs for routine random-access real-time use in a general clinical setting.

Cytokines as Immunological Markers for Systemic Inflammation in Dogs with Pyometra

Pyometra is a disease in dogs caused by bacterial infection of the uterus and resulting in SIRS (systemic inflammatory response syndrome) in nearly 6 of 10 cases. Clinical diagnostic criteria for SIRS are relatively unspecific, and biomarkers for the diagnosis of pyometra and SIRS in dogs are needed. Serum samples from 32 dogs were used in this study and grouped into dogs with pyometra and SIRS, dogs with pyometra without SIRS and healthy controls. The serum concentrations of IFN-γ, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18 and TNF-α were measured using multiplex analyses. The serum concentrations of CRP (C-reactive protein) were determined using sandwich ELISA. IL-7, IL-8, IL-15, IL-18 and TNF-α were detected in >94% of samples. IL-10 was detected in 28% of samples, and IL-4, IL-6 and IFN-γ were undetectable. Higher serum concentrations of IL-7 (p < 0.05) were detected in SIRS-positive dogs with pyometra (n = 13) as compared with healthy controls (n = 11). The concentrations of IL-8 were higher in SIRS-positive dogs with pyometra compared to the SIRS-negative group (n = 8; p < 0.05). Positive correlations of IL-15 with IL-18 (p < 0.0001) and with the concentrations of IL-7 (p < 0.0001 for both) were found, although there was no significant difference between groups. Furthermore, IL-15 correlated with concentrations of CRP (p < 0.05), which were higher in dogs with pyometra compared to controls (p < 0.0001). Our data suggest a role of several cytokines in the development of a systemic disease in dogs with pyometra and a possible diagnostic value for serum CRP, IL-7, IL-15 and IL-18 in canine SIRS caused by pyometra.