Endogenous serum insulin concentration in dogs with diabetic ketoacidosis

Objective: To determine endogenous serum insulin concentration in dogs with diabetic ketoacidosis (DKA), and to compare it to endogenous serum insulin concentration in diabetic dogs with ketonuria but no acidosis (KDM), diabetic dogs with uncomplicated diabetes mellitus (DM) that did not have ketonuria or acidosis, and dogs with non‐pancreatic disease (NP). Design: Prospective study. Setting: Veterinary Hospital of the University of Pennsylvania. Animals: Forty‐four client‐owned dogs; 20 dogs with newly diagnosed diabetes mellitus (7 dogs with DKA, 6 dogs with KDM, and 7 dogs with DM) and 24 dogs with non‐pancreatic disease. Interventions: Blood and urine samples were obtained at the time of admission to the hospital. Measurements and main results: Signalment, clinical signs, physical examination findings, and concurrent disease were recorded for all dogs. Blood glucose concentration, venous blood pH, venous blood HCO3^? concentration, urinalysis, and endogenous serum insulin concentration were determined in all dogs. Dogs with DKA have significantly decreased endogenous serum insulin concentrations compared to dogs with DM (P = 0.03) and dogs with non‐pancreatic disease (P = 0.0002), but not compared to dogs with KDM (P = 0.2). Five of 7 dogs with DKA had detectable endogenous serum insulin concentrations, and 2 of these dogs had endogenous serum insulin concentration within the normal range. Conclusions: Diabetic dogs with ketoacidosis have significantly decreased endogenous serum insulin concentration compared to dogs with uncomplicated diabetes mellitus. However, most dogs with DKA have detectable endogenous serum insulin concentrations, and some dogs with DKA have endogenous serum insulin concentrations within the normal range.     

Evaluation of plasma-ionized magnesium concentration in 122 dogs with diabetes mellitus: a retrospective study

The goal of this study was to evaluate plasma-ionized magnesium (iMg2+) concentration in a large group of dogs with naturally occurring diabetes mellitus and to determine whether dogs with diabetes mellitus have hypomagnesemia, as reported in diabetic humans and cats. Plasma iMg2+ concentrations were retrospectively evaluated at the time of initial examination of 122 diabetic dogs at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania. Diabetic dogs were defined as having uncomplicated diabetes mellitus (DM, 78 dogs) diabetic ketoacidosis (DKA, 32 dogs), or ketotic nonacidotic diabetes mellitus (DK, 12 dogs) on the basis of presence or absence of metabolic acidosis or ketonuria. Twenty-two control dogs were used to determine reference values for plasma iMg2+ concentration in healthy dogs. Plasma iMg2+ concentration also was evaluated in 19 nondiabetic dogs with acute pancreatitis because many of the dogs with DKA had concurrent acute pancreatitis. Plasma iMg2+ concentration was significantly higher in dogs with DKA (median 0.41 mmol/L, reference range 0.14-0.72 mmol/L) than in dogs with DM (0.33 mmol/L, 0.17-0.65 mmol/L; P = .0002) or the control group (0.32 mmol/L, 0.26-0.41 mmol/L; P = .006). There were no significant differences between plasma iMg2+ concentrations in dogs with DM or DK compared with control dogs. We conclude that dogs with naturally occurring diabetes mellitus do not have marked hypomagnesemia on initial examination at a tertiary care center.     

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type‐1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type‐2 DM. Hypothesis/Objectives: Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Animals: Twelve cats with DKA and 7 cats with uncomplicated DM. Methods: Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Results: Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Conclusions and Clinical Importance: Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.     

Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM.     

Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease

Cytokines have been associated with the progression of congestive heart failure (CHF) in humans and may be implicated in the pathophysiology of myxomatous mitral valve disease (MMVD) in dogs. The aim of this study was to determine the serum concentrations of cytokines in dogs with MMVD. The study included 16 Cairn terriers with no or minimal mitral regurgitation (MR), 41 Cavalier King Charles Spaniels (CKCS) with different degrees of MR and 11 dogs of different breeds with CHF due to MMVD. Granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, keratinocyte-derived chemokine, interferon-γ-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7 decreased with increasing left atrial size and IL-7 also decreased with increasing MR. IL-8 decreased with increasing left ventricular end-systolic internal dimensions. MCP-1 was increased in CHF dogs compared to healthy control dogs and IL-2, IL-7 and IL-8 decreased with increasing indices of disease severity. The results suggest a role for these cytokines in canine MMVD and CHF.     

Serum total and ionized magnesium concentrations and urinary fractional excretion of magnesium in cats with diabetes mellitus and diabetic ketoacidosis

OBJECTIVE: To determine magnesium (Mg) status in cats with naturally acquired diabetes mellitus (DM) and diabetic ketoacidosis (DKA), evaluate changes in Mg status after treatment for DKA, and correlate Mg status with systemic blood pressure and degree of glycemic control. DESIGN: Case series and cohort study. ANIMALS: 12 healthy cats (controls), 21 cats with DM, and 7 cats with DKA. PROCEDURE: Serum total magnesium (tMg) and ionized magnesium (iMg) concentrations and spot urinary fractional excretion of magnesium (FEmg) were determined, using serum and urine samples obtained from all cats when they were entered in the study and from cats with DKA 12, 24, and 48 hours after initiating treatment. Indirect blood pressure and degree of glycemic control were determined in 10 and 21 cats with DM, respectively. RESULTS: Initially, 2 and 13 cats with DM and 1 and 4 cats with DKA had serum tMg and iMg concentrations, respectively, less than the low reference limit (mean-2 SD) determined for controls. In cats with DKA, serum tMg concentration decreased significantly over time after initiating treatment. Urinary FEmg was significantly higher in cats with DM or DKA, compared with controls. Systemic hypertension was not detected nor was there a correlation between Mg status and degree of glycemic control in cats with DM. CONCLUSIONS AND CLINICAL RELEVANCE: Hypomagnesemia was a common finding in cats with DM and DKA and was more readily identified by measuring serum iMg concentration than tMg concentration. The clinical ramifications of hypomagnesemia in such cats remain to be determined.     

Accuracy of serum beta-hydroxybutyrate measurements for the diagnosis of diabetic ketoacidosis in 116 dogs

The aim of this study was to evaluate the accuracy of serum beta-hydroxybutyrate (beta-OHB) measurements for the diagnosis of diabetic ketoacidosis (DKA) in dogs. One hundred sixteen diabetic dogs were prospectively enrolled in the study: 18 insulin-treated (IT) diabetic dogs that had a positive urine ketone test and 88 untreated, newly diagnosed diabetic dogs. Venous blood gas tensions and pH, serum glucose and urea nitrogen (SUN), and electrolyte (Na+, Cl-, and K+) and urine acetoacetate (AA) concentrations were measured concurrently with serum beta-OHB concentrations. On the basis of laboratory findings, the patients were assigned to I of 3 groups: diabetic ketoacidosis (n = 43); diabetic ketosis (DK, n = 41); and nonketotic diabetes (NDK, n = 31). Serum beta-OHB concentrations differed significantly (P < .001) among the study groups. Although marked differences in beta-OHB concentrations were found, a considerable overlap exists between the distributions of dogs with DK and those with DKA. The overall accuracy of beta-OHB determination as a diagnostic test for DKA, determined by the area under the receiver operating characteristic (ROC) curve, was 0.92. In the 1.9- to 4.8-mmol/L range, serum beta-OHB determination sensitivity varied from 100 to 35.7%, whereas specificity varied from 39 to 100%. The cutoff value of 3.8 mmol/L showed the best equilibrium between specificity (95%), sensitivity (72%), and likelihood ratio (14.8). We concluded that the quantitative measurement of serum beta-OHB may be a potential tool for diagnosing and monitoring ketosis and ketoacidosis in diabetic dogs.     

Outcome of dogs with diabetic ketoacidosis: 127 dogs (1993-2003)

The aim of this study was to retrospectively describe the outcome of 127 dogs with naturally occurring diabetic ketoacidosis (DKA) and to examine the association between outcome of canine DKA and clinical and clinicopathologic findings. Eighty-two (65%) dogs were diagnosed with DKA at the time of initial diagnosis of diabetes mellitus (DM). Eighty-seven dogs (69%) had one or more concurrent disorders diagnosed at the time of hospitalization. Commonly identified concurrent conditions included acute pancreatitis (52, 41%), urinary tract infection (21, 20%), and hyperadrenocorticism (19, 15%). Dogs with coexisting hyperadrenocorticism were less likely to be discharged from the hospital (P = .029). Of 121 treated dogs, 89 dogs (70%) survived to be discharged from the hospital, with a median hospitalization of 6 days. Nonsurvivors had lower ionized calcium concentration (P < .001), lower hematocrit (P = .036), lower venous pH (P = .0058), and larger base deficit (P = .0066) than did survivors. Time from admission to initiation of subcutaneous insulin therapy was correlated with lower serum potassium concentration (P = .0056), lower serum phosphorus concentration (P = .0043), abnormally high white blood cell count (P = .0060), large base deficit (P = .0015), and low venous pH (P < .001). Multivariate analysis showed that base deficit was associated with outcome (P = .021). For each unit increase in the base deficit, there was a 9%) greater likelihood of discharge from the hospital. In conclusion, the majority of dogs with DKA were not previously diagnosed with DM. Concurrent conditions and electrolyte abnormalities are common in DKA and are associated with length of hospitalization. Survival was correlated to degree of anemia, hypocalcemia, and acidosis.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Evaluation of plasma inflammatory cytokine concentrations in racing sled dogs

In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans.     

A retrospective study of serum β-hydroxybutyric acid in 215 ill cats: clinical signs, laboratory findings and diagnoses

Serum concentrations of β-hydroxybutyric acid (sBHBA) are increased in cats with diabetes mellitus (DM), diabetic ketoacidosis (DKA) and hepatic lipidosis (HL). This study assessed sBHBA as a diagnostic tool in 215 consecutively-enrolled ill cats in the general population in a veterinary hospital. At the time of presentation, sBHBA was within the reference range in 158/215 (73.5%) cats (median 0.27; range 0.00-0.49 mmol/L) and elevated in 57/215 (26.5%) cats (median 0.87; range 0.51-21.45 mmol/L). Compared to cats with normal sBHBA, those with increased sBHBA had higher frequencies of anorexia, weight loss, icterus, polyuria/polydipsia, hyperbilirubinaemia, hypertriglyceridaemia, pancreatitis, HL, DM and DKA. They had higher concentrations of bilirubin and triglycerides and lower concentrations of potassium, chloride and total protein. There were positive correlations (P<0.01) between sBHBA and urinary glucose (r=0.42) and ketones (r=0.76), but there were no group differences in dipstick levels of urinary ketones. Cats with DM/DKA and with HL had significantly higher sBHBA compared to other cats. Receiver operator characteristics analysis of sBHBA as a predictor of HL showed that sBHBA was a good predictor of HL. Increased sBHBA occurs frequently in ill cats and provides useful diagnostic information, especially in DM/DKA and HL.     

The impact of weight loss on circulating cytokines in Beagle dogs

Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory and chemotactic cytokines that are contributing to insulin resistance and related co-morbidities. Cytokines act in networks and exhibit pleiotropic effects so we investigated the circulating levels of a wide array of cytokines (pro and anti-inflammatory, chemotactic and growth factors) in a canine model of weight loss. The dogs served as their own control in order to study the impact of weight loss independent of potential confounding factors, such as history of excess weight or gender. While low-grade inflammation had been previously investigated in obese dogs by measuring changes in adipokines, acute phase proteins and key pro-inflammatory cytokines, to the best of our knowledge this is the first study to evaluate how weight loss impacts a wide array of circulating cytokines.Eighteen overweight Beagle dogs were recruited (six spayed females and 12 neutered males), and none of them were grossly obese according to the body condition score (BCS). All the dogs reached an ideal weight by the end of the program. Parameters were assessed before (baseline), at mid-point (month 3) and at end-point (month 6). Plasma GM-CSF, IL-2, Il-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IFNγ, IP-10, TNFα, monocyte chemotactic protein 1 (MCP-1), keratinocyte chemokine (KC) were measured with canine multiplex immunoassays. Fat mass was assessed by dual energy X-ray absorption (DEXA).Several cytokines decreased throughout the weight loss program (p < 0.01) and were correlated with the percentage of fat measured by DEXA (p < 0.05): chemotactic (MCP-1), growth factors (GM-CSF, IL-7 and IL-2), and pro-inflammatory (KC and IL-18). We could not show trends for several cytokines, possibly because their level may be lower than the assay sensitivity: anti-inflammatory (IL-4 and IL-10), and pro-inflammatory (IL-6 and TNFα).In conclusion, while our findings for several pro-inflammatory and chemotactic cytokines are in accordance with human and rodent studies, we may have identified additional cytokines, such as growth factors, related to obesity-induced low-grade inflammation. Considering the weight loss was enabled by an adjusted diet, the role of this association of cytokines in insulin resistance and related co-morbidities needs to be clarified. Our results could help better understand the cytokine biology in dogs, and as such are relevant for further elucidating the relationship between immune function and metabolism/nutrition.     

Quantification of mRNA encoding cytokines and chemokines in nasal biopsies from dogs with sino-nasal aspergillosis

Canine sino-nasal aspergillosis is usually caused by Aspergillus fumigatus and is similar to human chronic erosive non-invasive fungal sinusitis. The pathogenesis of the disease is poorly understood. We investigated the nature of the local immune response mounted in canine sino-nasal aspergillosis. Quantitative RT-PCR was carried out on RNA isolated from nasal biopsies from diseased and control dogs, using specific assays designed to amplify mRNA encoding a panel of cytokines and chemokines. Canine sino-nasal aspergillosis was associated with significantly increased expression of mRNA encoding MCP-1, -2, -3 and -4, IL-8, IL-10, IL-18 and TNF-alpha relative to controls (P<0.01) but there was no difference between groups with respect to IL-4, IL-5, IL-6, IL-12, TGF-beta, and eotaxin-2 and -3. The up-regulation of proinflammatory cytokines and chemokines related to the influx of phagocytic cells might account for the localisation of this infection to the upper respiratory tract. The up-regulation of the expression of the immunomodulatory cytokine IL-10 in nasal tissue from affected dogs might be important in limiting the extent of local tissue destruction, but might also account for the fact that infected dogs are generally unable to clear this infection spontaneously.     

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.     

Measurement of serum interleukin-10 in the dog

The objective was to evaluate independently the reliability of a commercially available canine serum interleukin-10 (IL-10) enzyme-linked immunoassay (ELISA) and to investigate canine serum IL-10 concentrations in healthy dogs, in dogs with a naturally-occurring acute phase reaction and in dogs following surgical stimulus by assessing intra- and interassay imprecision, inaccuracy and detection limits. Median (and range) serum IL-10 concentrations (ng/L) in the various groups were as follows: healthy dogs (n=15), 18.9 (11.2-71.5); dogs with pyometra (n=9), 37.9 (12.4-201.8); dogs with angiostrongylosis (n=8), 20.29 (14.3-108.7) and values in dogs following surgical stimulus (n=15), 14.8 (10.7-65.8). The assay measured canine serum IL-10 reliably (intra- and interassay imprecision 4.9-8.3% and 9.9-10.9%, respectively; detection limit 10.7 ng/L with no significant inaccuracy). No significant increases in IL-10 were observed following surgical stimulus and no difference in IL-10 was observed between the diagnostic groups. IL-10 values showed a higher degree of variation in dogs with an inflammatory response, i.e. those with elevated serum C-reactive protein (CRP) concentrations, compared to healthy dogs. As anticipated, healthy dogs had low levels of both analytes, whereas dogs with an acute phase response had IL-10 levels with no clear relationship to CRP concentrations, with observed low IL-10 values even when there was a marked inflammatory response.     

Elevated Plasma Levels of Interleukin 1β, Tumour Necrosis Factor α and Monocyte Chemotactic Protein 1 Are Associated with Pregnancy Toxaemia in Ewes

Pregnancy toxaemia is a metabolic disorder that results from an inadequate energy supply to the growing maternal–fetal unit. The mechanism underlying the pathogenesis of the syndrome has not been fully clarified; however, a key role for cytokines and chemokines including interleukin 1 β (IL-1β), tumour necrosis factor α (TNF-α) and monocyte chemotactic protein 1 (MCP-1) has been indicated in women and experimental animals. However, information on the maternal plasma levels of IL-1β, TNF-α and MCP-1 in ewes with pregnancy toxaemia is limited. Thus, the present study was designed to determine plasma IL-1β, TNF-α and MCP-1 concentrations in ewes with severe (n = 6) and mild (n = 4) naturally occurring pregnancy toxaemia and in uncomplicated pregnant ewes (n = 10) using enzyme-linked immunosorbent assay (ELISA). All ewes with pregnancy toxaemia had significantly lower body temperature and respiratory rate than uncomplicated pregnant ewes (p < 0.05). With the highest concentrations in severe cases, heart rate, proteinuria and serum uric acid levels as well as plasma IL-1β, TNF-α and MCP-1 were significantly different among all three groups (p < 0.05). The plasma concentrations of IL-1β in control ewes and ewes with mild and severe toxaemia were 15.81 ± 3.90 pg/ml, 23.83 ± 2.42 pg/ml and 34.55 ± 8.03 pg/ml, respectively. The plasma concentrations of TNF-α in control ewes and ewes with mild and severe toxaemia were 7.71 ± 1.61 pg/ml, 16.13 ± 3.63 pg/ml, and 22.85 ± 3.64 pg/ml, respectively. The plasma concentrations of MCP-1 in control ewes and ewes with mild and severe toxaemia were 101.70 ± 9.86 pg/ml, 134.75 ± 6.24 pg/ml, and 157.67 ± 9.69 pg/ml, respectively. Moreover, plasma IL-1β, TNF-α and MCP-1 levels were positively correlated with clinical and well-establish biochemical parameters of pregnancy toxaemia, serum uric acid and proteinuria (p < 0.01). Concomitant increase of plasma IL-1β, TNF-α and MCP-1 concentrations along with serum uric acid, proteinuria, and worsening of the clinical signs indicates that such cytokines are involved in the aetiopathogenesis and in perpetuation of the local and systemic inflammatory reactions in pregnancy toxaemia in ewes. Hence, plasma IL-1β, TNF-α and MCP-1 may potentially serve as markers to monitor prognosis of pregnancy toxaemia in ewes.