Systemic and eosinophilic lesions in rats with spontaneous eosinophilia (mes rats)

The mes rat is from an inbred mutant colony of rats with spontaneous eosinophilia. In order to investigate the pathogenesis of the mes rat, the histopathology and hematology for 76 mes rats were examined at several weeks of age. Tissue eosinophilia developed at 8 weeks of age when the blood eosinophil was 500 cells per microliter or more. Subsequently, eosinophilia progressed with age, and splenic eosinophilopoiesis and erythropoiesis appeared simultaneously. Many inflammatory lesions were induced after 10 weeks of age when the blood eosinophils became 1,000 cells per microliter or more. Gastroenteritis and mesenteric lymphadenitis were seen in 44 of 47 (94%) and 31 of 47 (66%) rats, respectively, after 10 weeks of age. Aortitis that deteriorated with age was found in 19 of 39 (49%) rats after 12 weeks of age. Hepatic fibrosis was found in four rats that exhibited severe eosinophilia and anemia. These results are comparable to the features of a hypereosinophilic syndrome in humans and other animals.     

Ultrastructural morphogenesis of 4-ipomeanol-induced bronchiolitis and interstitial pneumonia in calves

The two objectives of this research were 1) to describe the ultrastructural morphogenesis of pulmonary damage and repair induced in calves after treatment with 4-ipomeanol and 2) to characterize infiltrating pulmonary inflammatory cells by bronchoalveolar lavage. Interstitial edema was observed as early as 4 hours after intravenous injection of 4-ipomeanol (5 mg/kg body weight) and progressed to severe alveolar edema by 72 hours. Damage to type I alveolar epithelial cells and terminal bronchiolar nonciliated cells included dilation of endoplasmic reticulum and perinuclear envelopes and was present at 4 hours after treatment. Necrosis and sloughing of these cells from basement membranes occurred at times from 12 to 96 hours after treatment. Alveolar capillary endothelial cells had mild dilation of endoplasmic reticulum at times from 12 to 72 hours after treatment. Necrosis of endothelial cells was not observed. Inflammatory cell infiltrates in bronchioles and alveoli were dominated by macrophages and neutrophils. Significant elevations (P less than 0.05) in numbers of neutrophils and macrophages were recovered by bronchoalveolar lavage at times from 24 to 96 hours after 4-ipomeanol-treatment. Hyperplasia of nonciliated bronchiolar epithelial cells and of type II alveolar epithelial cells were observed at 72 and 96 hours after treatment. The results indicate that type I alveolar epithelial cells and nonciliated bronchiolar epithelial cells are most susceptible to 4-ipomeanol-induced damage and necrosis in calves. 4-ipomeanol-induced pulmonary edema in calves occurs prior to ultrastructurally-demonstrable, mild, alveolar capillary endothelial cell damage.     

Intraperitoneal Circulation and Drainage in the Dog

The patterns of dispersion and drainage of a low viscosity, oil-based contrast medium within the peritoneal cavity were examined in 12 normal dogs. Intraperitoneal injection of contrast medium was cranial or caudal and drainage was by the sump-Penrose or open peritoneal method. Radiographs were made over a 96 hour period, before and after peritoneal drainage was established. Each dog was euthanatized and necropsied. The contrast medium was dispersed throughout the peritoneal cavity 15 to 30 minutes after cranial injection and 1 to 2 hours after caudal injection. Most of the contrast medium drained within 6 hours after open peritoneal drainage and within 24 to 48 hours after sump-Penrose drainage. At necropsy, there was complete encasement of all sump-Penrose drains and partial occlusion of all open peritoneal incisions by omentum adhered to the abdominal wound edges. Peritonitis was not grossly evident, but all dogs showed histologic evidence of an acute inflammatory reaction associated with the drain or wound edge.     

Pulmonary Eosinophilia Associated with Increased Airway Responsiveness in Young Racing Horses

Horses are known to acquire small airway disease (SAD), an allergen-induced naturally occurring syndrome of reversible obstructive lung disease accompanied by airway hyperresponsiveness and increased inflammatory cell numbers on bronchoalveolar lavage (BAL). This disorder has received scant attention in young racehorses. The purpose of the present report was to examine the effect of BAL eosinophilia in young racehorses on clinical examination, BAL, hematology, airway responsiveness, and on pulmonary function at rest and after a standardized exercise challenge. Five (3 males, 2 females; age 2.6 ± 0.9 years) with a history of respiratory compromise and BAL eosinophil differential count <5% and 6 controls (4 males, 2 females; age 3.5 ± 1.0 years) training and performing to expectation with normal BAL cell differential (eosinophils < 1%) were studied. Respiratory system clinical examination was performed and expressed as a clinical score. Arterial blood gas measurements, CBC, and pulmonary function testing were performed at rest. Pulmonary mechanics measurements were repeated 1 hour and 20 hours after a standardized treadmill exercise challenge. Incremental histamine inhalation challenge was performed and the concentration of histamine effecting a 35% decrease in dynamic compliance (PC35C_Dyn) was determined. Significant differences were noted between and controls with regard to clinical score ( P = .01), blood eosinophils ( P = .04), BAL cell count ( P = .04), BAL macrophage differential ( P = .04), PC35C_Dyn ( P = .008), and tidal volume and respiratory rate at 20 hours following exercise challenge ( P = .05). We conclude that pulmonary eosinophilia and airway hyperresponsiveness are manifest in some young horses without overt airway obstruction at rest. We speculate that these may be early events in the natural progression of heaves.     

Dermal responses to Ostertagia ostertagi in Ostertagia ostertagi- and Cooperia punctata-inoculated calves

Calves harboring patent Ostertagia ostertagi or Cooperia punctata were given intradermal injections of O ostertagi 3rd-stage larval antigen. The initial injections were followed 30 days later by a 2nd series of injections. Skin thickness was measured at injection sites for 72 hours after injection. Selected injection sites including saline solution control sites were biopsied at 30 minutes, at 3, 24, 48, and 72 hours, and at 30 days after injection. After the 1st series of injections, there was a clear distinction in dermal reactions between O ostertagi-inoculated calves and C punctata-inoculated calves; after 24 hours, reactions were not seen in the C punctata-inoculated calves. Marked dermal reactions occurred in the O ostertagi-inoculated calves. The reactions at 30 minutes and 3 hours were characterized by slight-to-extensive infiltration of neutrophils and dermal edema. The 24-hour cellular reaction was principally due to neutrophil and eosinophil infiltration with edema and necrosis. Reactions at 48 to 72 hours were due to eosinophils and perivascular accumulations of macrophages and lymphocytes. Necrosis, neutrophils, and edema were present in foci where fragments of nematodes were located. On reinjection, a clear distinction in dermal reactions between calves was not seen based on the type of nematode infection. Thirty days after dermal inoculation, large nodules developed at the site of the initial antigen injection. The nodules were characterized by marked intradermal proliferation of lymphocytes in a follicular pattern with occasional macrophages and rare multinucleated giant cells.     

Stability of hematologic analytes in monkey, rabbit, rat, and mouse blood stored at 4°C in EDTA using the ADVIA 120 hematology analyzer

Background: The time from sampling to analysis can be delayed when blood samples are shipped to distant reference laboratories or when analysis cannot be readily performed. Objective: The objective of this study was to evaluate the stability of hematologic analytes in blood samples from monkeys, rabbits, rats, and mice when samples were stored for up to 72 hours at 4°C. Methods: Blood samples from 30 monkeys, 15 rabbits, 20 rats, and 30 mice were collected into EDTA‐containing tubes and were initially analyzed within 1 hour of collection using the ADVIA 120 analyzer. The samples were then stored at 4°C and reanalyzed at 24, 48, and 72 hours after collection. Results: Significant (P<.0003) changes in hematologic analytes and calculations included increased HCT and MCV and decreased MCHC and cell hemoglobin concentration mean (CHCM) at 72 hours and increased MPV at 24 hours in monkeys; increased MCV at 72 hours and MPV at 48 hours and decreased monocyte count at 24 hours in rabbits; increased MCV and decreased MCHC, CHCM, and monocyte count at 24 hours in rats; increased MCV, red cell distribution width, and MPV and decreased MCHC, CHCM, and monocyte count at 24 hours in mice. Conclusions: Although most of the changes in the hematologic analytes in blood from monkeys, rabbits, rats, and mice when samples were stored at 4°C were analytically acceptable and clinically negligible, the best practice in measuring hematologic analytes in these animals is timely processing of blood samples, preferably within 1 hour after collection.     

Induction of tissue eosinophilia by platelet-activating factor in Merino sheep.

A study was undertaken on the capacity of platelet-activating factor (PAF) to induce eosinophil accumulation in the mammary glands of non-lactating sheep. Platelet-activating factor induced dose-dependent accumulation of eosinophils in mammary exudates 24 h after infusion. Infection, by intraruminal injection of 20,000 infective Trichostrongylus colubriformis larvae, did not modify the responsiveness of outbred sheep to intramammary infusion of PAF. Mature ewes from high and low responder lines of a flock of sheep, selected on the basis of their responses to vaccination and experimental challenge with T. colubriformis as lambs, did not differ in the magnitude of the eosinophil responses to doses of PAF from 5 x 10(-13) to 5 x 10(-7) mol per gland. Intramammary infusion of an extract from third stage larvae of Haemonchus contortus elicited inflammatory exudates containing five- to ten-fold more eosinophils than that elicited by the highest dose of PAF tested. The experiments indicate that the eosinophil chemotactic agonist PAF can induce tissue eosinophilia in sheep and thus may play a role in directing the accumulation of eosinophils in tissues during disease states such as gastrointestinal parasitism.     

Haematological and immunological response of unrestrained cattle to Psoroptes ovis, the sheep scab mite

Cows were infected twice with 600 and 500 nymphs and adults of a bovine strain of Psoroptes ovis with a nine-week interval. The haematological response and the non-specific mitogen- and antigen-induced responsiveness of the peripheral blood lymphocytes of the animals was followed. Dermal reactivity to P ovis antigen injection was studied five weeks after reinfection. After the first infection with 600 mites none of the infected animals developed clinical psoroptic mange but a leucocytosis developed, contributed to primarily by an eosinophilia and by a slight lymphocytosis. Antigen-induced lymphocyte blastogenesis was used to measure the antigen-sensitive cell population in peripheral blood and this population showed a maximum increase 10 days after infection; however, antigen-sensitive cells remained above normal levels until reinfection. Upon challenge infection with 500 mites the infected animals showed an immediate hypersensitivity type reaction with a marked pruritus, scratching and exudation. Thereafter the lesions healed rapidly and none of the animals developed clinical mange. This clinical reaction was accompanied by a secondary eosinophilia but no change was apparent in the other blood elements. A marked increase in the blastogenic response of the peripheral blood lymphocytes was also apparent and this peaked three weeks after challenge. Following the intradermal injection of P ovis antigen there was an immediate swelling of the injection site in all infected and control animals and skin thickness was maximal one hour after injection. Thereafter there was a clear distinction in dermal reactions between P ovis infected and control animals; after 48 hours reactions were not seen in the control animals while marked dermal reactions were still present in the P ovis infected group.     

Histochemical identification of tissue eosinophils in the inflammatory response of the fowl (Gallus domesticus)

A staining technique was developed for the differential identification of tissue eosinophil and heterophil leucocytes in the fowl. Pieces of formalin-fixed skin, challenged with dinitrochlorobenzene (DNCB) or citraconic anhydride (CA), were incubated in a substrate suitable for peroxidase prior to embedding in either paraffin wax, glycol methacrylate or Araldite. This results in deep brown staining of the eosinophil granules while those of the heterophils remain unstained. Heterophils and eosinophils were conspicuous at 30 minutes after challenge in the early inflammatory response. By 48 hours the heterophilic response had diminished and eosinophils had almost disappeared. Only mononuclear cells were seen at 72 hours. It is suggested that the eosinophil leucocyte might act as an early modulator of inflammation in delayed-type hypersensitivity responses in the fowl.     

Investigations on the role of staphylococci in the pathogenesis of German shepherd dog pyoderma (GSP)

Skin reaction patterns to intradermal injections of a Staphylococcus intermedius antigen were examined in physically healthy dogs and in dogs with German Shepherd dog Pyoderma (GSP) at 15 and 30 minutes and at 1, 2, 4, 6, 8, 24, 48 and 72 hours after the injection. In both groups the skin histopathology revealed an aspecific inflammatory response of an early polymorphonuclear reaction, followed by a mononuclear cell reaction at 24 and 48 hours. It is concluded that hypersensitivity to staphylococcal antigens does not play a role in the pathogenesis of GSP.     

Concentration of ivermectin in bovine serum and its effect on the fecundity of psoroptic mange mites

The concentration-time profile of ivermectin in serum was determined for 3 Hereford heifers. The mean maximum serum concentration, 29 ng of ivermectin/ml, was obtained 48 hours after single subcutaneous injection of 200 micrograms/kg of body weight. The fecundity of mites placed on 9 treated animals at 5, 9, 12, 15, 18, and 21 days after injection was reduced by 96% to 99%. At 24 days after treatment, when serum concentration had decreased to about 2 ng/ml, the capability of mites to produce eggs increased to 50% of mites from nontreated calves. At 27 and 30 days after the drug was injected, egg production by mites on treated calves was equivalent to that of mites on nontreated calves. The reduced fecundity resulted from an almost complete cessation of oviposition by females after only a 1-day exposure to ivermectin-treated calves.     

Response of plasma corticosteroids and circulating leukocytes in cattle following intravenous injection of different doses of adrenocorticotropin.

The relationships among exogenous adrenocorticotropin (ACTH), plasma corticosteroids, and circulating leukocytes were studied in 7 lactating cows. Blood samples were obtained from jugular cannulas at -2, -1, and 0 hours before ACTH was injected (base line) and 0.25, 0.50, 1, 2, 3, 6, and 24 hours after injection. Plasma corticosteroids were increased progressively by injecting doses of ACTH between 1 and 200 IU. Plasma corticosteroids reached peak concentrations between 15 and 30 minutes and returned to base line within 1 to 3 hours after 1, 5, and 10 IU doses of ACTH were injected, but required as long as 6 hours after injection of 100 and 200 IU. Base line counts of circulating leukocytes averaged 7.3 X 10(3) cells/mm3 and remained unchanged after injecting 0 and 1 IU of ACTH (P less than 0.05). Significant dose-dependent increases in circulating leukocytes were detected within 2 hours after administering 5, 10, and 100 IU of ACTH. Responses to 100 and 200 IU were similar. The average concentration of leukocytes increased up to 6 hours after ACTH administration and returned to base line values within 12 to 24 hours in cows injected with 5 and 10 IU, but not until 48 hours in cows injected with 100 and 200 IU of ACTH. In contrast to the delayed and sustained responses observed for leukocytes, corticosteroid responses were rapid and transient. Moreover, the administration of 200 IU of ACTH was considered to increase circulating corticosteroids and leukocytes beyond that found in dairy cattle exposed to stress associated with overmilking, acute coliform mastitis, or parturition.     

Motility and Fertility Evaluation of Thawed Frozen Stallion Semen After 24 Hours of Cooled Storage

Breeding mares with cryopreserved semen requires specialized equipment for storage and thawing and more intensive mare management. The objectives of this study were (1) evaluate the longevity of frozen stallion semen once it had been thawed, extended, and maintained at 5°C for 48 hours in a passive cooling container, and (2) determine fertility potential of frozen semen that had been thawed, extended, and used to inseminate mares after 24 hours of cooled storage. Eight ejaculates were collected and aliquots were cooled in either INRA96 and CryoMax LE minus cryoprotectant at a concentration of 50 million total sperm/mL. The remainder of the ejaculate was frozen in CryoMax LE extender at a concentration of 200 million total sperm/mL. Semen was thawed using 1 of 3 thawing protocols, and diluted to a concentration of 50 million total sperm/mL in either INRA96 or CryoMax LE minus cryoprotectant and cooled to 5°C. Sperm motility was evaluated at 24 and 48 hours. Eight mares were inseminated over two estrous cycles using frozen semen that had been thawed, extended in INRA96, and cooled for 24 hours. There was no difference in progressive motility at 24 or 48 hours of cooled-storage post-thaw between the 3 thawing protocols. An overall per cycle pregnancy rate of 56% (9/16 cycles) was achieved using frozen-thawed semen that had been extended and cooled for 24 hours. In summary, frozen stallion sperm was thawed, extended, and cooled to 5°C for 24 hours and still maintained adequate (>30%) sperm motility and fertility.     

The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the macroscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.     

Serum and tissue concentrations of erythromycin in calves with induced pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of erythromycin administered IM and the tissue concentration changes with time were evaluated in 2-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures through the thoracic wall into each lung. Six days prior to induction of pneumonia, erythromycin (15 mg/kg) was administered in a single IM dose. Erythromycin was administered again 48, 72, and 96 hours after injection of P haemolytica. On the third day of erythromycin administration (96 hours), the calves were serially euthanatized in groups of 4 calves each at 2, 5, 8, 12, 18, and 24 hours after the final dose was given. Tissue concentrations of erythromycin in kidney, liver, lung, muscle, CSF, and serum were determined. Neither the serum concentrations nor the overall pharmacokinetic values were significantly (P less than or equal to 0.05) changed by pneumonia. The concentrations of erythromycin were maximal at 5 hours for liver, muscle, and serum and at 8 hours for CSF, kidney, and lung. Serum and muscle concentrations were similar, whereas concentrations in CSF were lower than in serum and higher in kidney, liver, and lung. The lung/serum ratios were approximately 2.5 to 3 at 8 through 24 hours after IM administration. The peak concentration in lung was approximately 6 micrograms/g at 8 hours.     

Atopy patch test reactions in high-IgE beagles to different sources and concentrations of house dust mites

Protocols for atopy patch testing (APT) were evaluated on six high-IgE dogs sensitized to house dust mites (HDM) using various concentrations and sources of HDM. Two sources of HDM were compared: Heska slurry and four concentrations of Greer HDM. Saline was used as a negative control. Patches were removed after 48 h and the sites evaluated at 0, 6, 24, 48, 72 and 96 h for erythema, macules, papules and pustules. Each sign was scored from 0 to 3 (0 = absent and 3 = severe). Total score was used for analysis. Mean total scores significantly increased for both Greer and Heska HDMs from 6 h, peaking at 48 h for G100 (100 mg mL(-1)), G300 and G668, and at 72 h for Heska and G31.25. Across all times, Heska HDM scores were significantly higher than those of G31.25 with the largest difference at 96 h. Heska scores, however, were significantly lower than those of other Greer concentrations (G100, G300 and G668) particularly at 96 h. No reactions were noted at saline sites. It is concluded that Greer-HDM at 100 mg mL(-1) is the most suitable concentration for APT in dogs because it induces reactions comparable if not higher than more concentrated HDM preparations.     

Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony

Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and portions of the pulmonary arteries and veins and right and left ventricles were prepared for scanning and transmission electron microscopy. In ponies that were given only LPS, some areas of pulmonary vascular endothelium appeared normal when compared with untreated controls, but other areas had disoriented endothelial cells or had varying amounts of sloughing, which ranged from focal areas of a few cells to large areas of denuded endothelium. Ponies treated with FM before LPS had less severe and less extensive endothelial cell damage. In both groups, leukocytes were attached to areas of the vessel wall; endothelial cell damage was greater in these regions. Administration of FM before LPS administration attenuated the LPS-induced endothelial cell damage.     

Effect of aspirin on ex vivo generation of thromboxane in healthy horses

Different dosages of aspirin were administered (by nasogastric tube) to 3 groups of 5 healthy adult horses to determine the minimal effective dosage needed to decrease serum thromboxane B2 (TxB2) concentrations and to determine the duration of this decrease. When compared with their base-line serum TxB2 concentrations, horses in group 1 (given 5 mg/kg) had a 71% decrease in TxB2 concentrations at 24 hours after aspirin was given and a 86% decrease at 48 hours; serum TxB2 concentrations were back to base-line values by 120 hours. Horses in group 2 (given 10 mg/kg) had a 60% decrease in TxB2 concentrations at 24 hours after aspirin was given, an 84% decrease at 48 hours, a 48% decrease at 96 hours, and an 18% decrease at 6 days. Horses in group 3 (given 20 mg/kg) had a 68% decrease in TxB2 concentrations at 24 hours, a 93% decrease at 72 hours, an 87% decrease at 96 hours, and a 70% decrease at 6 days after aspirin treatment was given. All groups had a statistically significant decrease in TxB2 concentrations (P less than 0.05) by 12 hours after aspirin was given, which persisted 96 hours for group 1 and throughout the study for groups 2 and 3. The maximal TxB2 decrease was similar among the 3 groups (90% decrease from base line), and there were no significant differences among the TxB2 concentrations between 24 and 72 hours after treatment was given.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intracameral injection of preservative-free lidocaine on the anterior segment of the eyes in dogs

OBJECTIVE: To evaluate effects of intracameral injection of preservative-free 1% and 2% lidocaine hydrochloride solution on the anterior segment of the eyes in dogs. ANIMALS: 16 adult healthy dogs (8 male and 8 female) judged to be free of ocular disease. PROCEDURE: Dogs were randomly assigned to 2 groups of 8 dogs each. Group 1 dogs received an intracameral injection of 0.10 mL of preservative-free 1% lidocaine solution in the designated eye, and group 2 dogs received 0.10 mL of preservative-free 2% lidocaine solution in the designated eye. After injection, intraocular pressure was measured every 12 hours for 48 hours and then every 24 hours until 168 hours after injection. Slit-lamp biomicroscopy was performed preceding intracameral injection, 8 hours after injection, and then every 24 hours until 168 hours after injection. Ultrasonic pachymetry and specular microscopy were performed preceding intracameral injection and 72 and 168 hours after injection. Corneal thickness and endothelial cell density and morphology were compared with baseline measurements. RESULTS: No significant differences were found in intraocular pressure, corneal thickness, endothelial cell density, and morphologic features in either group, compared with baseline. A significant difference in aqueous flare was found for treated and control eyes 8, 24, and 48 hours after injection, compared with baseline. No significant difference in aqueous flare was found between treated and control eyes within either group. CONCLUSIONS AND CLINICAL RELEVANCE: No adverse ocular effects were detected after intracameral injection of preservative-free 1% or 2% lidocaine solution; thus, its use would be safe for intraocular pain management in dogs.     

Effect of Intramammary Infusion of Tumour Necrosis Factor‐α on Milk Protein Composition and Induction of Acute‐Phase Protein in the Lactating Cow

The present study was designed to evaluate the effects of tumour necrosis factor‐α (TNF‐α) on lactating bovine mammary functions such as milk protein secretion and the integrity of the milk‐blood barrier. The effect on the induction of the systemic inflammatory response was also examined using concentrations of serum haptoglobin (Hp), a major inflammatory acute‐phase protein, as an index. One hundred micrograms per mammary gland of recombinant bovine (rBo) TNF‐α or placebo saline was individually infused into a rear mammary gland of each of four lactating cows, and milk and blood samples were collected before and 4, 8, 24, 32, 48, 96 and 168 h after infusion. In the rBoTNF‐α‐infused gland, increases of somatic cell counts were observed at 4–48 h. Although concentrations of total milk protein were not changed, compositions of milk proteins varied following rBoTNF‐α infusion. Concentrations of caseins, α‐lactalbumin and β‐lactoglobulin were significantly decreased at 4 and 8 h. Lactoferrin concentrations were significantly increased at 4 h. Significant infiltrations of serum albumin, immunoglobulin G1 (IgG1) and IgG2 were observed at 4 and 8 h. Elevations of the serum concentration of Hp were detected at 8‐32 h, but were very small in comparison with those reported in inflammatory diseases. Changes in rectal temperature and white blood cell counts were not significant. These results show that single rBoTNF‐α infusion into the lactating mammary gland suppresses the lactogenic function of the gland and influences the function of the milk‐blood barrier, with little effect on the generalized inflammatory response.