Experimental acute canine monocytic ehrlichiosis: clinicopathological and immunopathological findings

Clinical signs, humoral and cellular immune responses, and microscopic and gross tissue alterations resulting from acute experimental Ehrlichia canis infection in dogs were studied. Four dogs were inoculated with E. canis and four were used as uninfected controls. After a 10-14-day incubation period, infected dogs developed pyrexia up to 41 degrees C for 6-8 days. Antibody titers to E. canis antigen were demonstrable in all inoculated dogs at 30 days post-infection. Necropsy of infected animals revealed pale mucous membranes, generalized lymphadenopathy, splenomegaly, edema and ascites. Microcopically, the main lesions were: lymphoreticular hyperplasia in cortical areas of lymph nodes and spleenic white pulp, periportal accumulation of mononuclear cells and centrolobular fatty degeneration of the liver. Kidneys presented with glomerulonephritis characterized by interstitial mononuclear infiltration. Immunophenotyping of lymphocytes from lymph nodes and spleen sections displayed alterations in IgG, IgM, CD3+ and CD8+ cells population in infected dogs.     

Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease.

Experimental infection with equine herpesvirus 1 (rhinopneumonitis) resulted in neurologic disease in 8 of 15 inoculated horses. Nonpregnant animals did not develop clinical disease, and microscopic examination of tissues revealed no changes. In all mares between 3 and 9 months of gestation, a neurologic syndrome appeared 6 to 8 days after inoculation. Mares inoculated when 10 months pregnant did not develop neurologic disorders, but several aborted. The histopathologic change common to both sequelae was vasculitis, involving smaller arteries and veins. Although blood vessel changes were detected in endometrium of all pregnant mares, vascular changes were present in the central nervous system only in mares having neurologic disease. Concomitant degeneration of nervous tissue occurred within the central nervous system and, in many sites, anatomic and temporal relationships of vasculitis and nervous tissue degeneration suggested a cause-effect relationship. This theory was strengthened by the lack of usual histopathologic indications of encephalomyelitis. In cerebrospinal fluid from affected mares, there was an increase in protein but not pleocytosis.     

Experimental babesiosis in coyotes and coydogs

One splenectomized and 6 intact coyotes (Canis latrans), and 2 coydogs were experimentally inoculated with a recent isolate of Babesia gibsoni. The disease was mild in intact animals, was fatal in the splenectomized coyote, and was characterized by a regenerative hemolytic anemia with the PCV decreasing to 16% in intact animals and to 6% in the splenectomized coyote. Peak parasitemia ranged from 3% to 21% of erythrocytes infected and was inversely correlated to PCV. Serum lactate dehydrogenase, bilirubin, and globulin concentrations were increased in all infected animals. Three weeks after inoculation, specific antibody titers increased to 1:65,536 and remained elevated in the chronically infected animals. The splenectomized coyote had progressive weakness until death, 24 days after inoculation. Intact animals had splenomegaly and anorexia at the height of infection. The splenectomized coyote had generalized edema, omental petechiae, renal and hepatic degeneration, membrano-proliferative glomerulonephritis and congestion, extramedullary hematopoiesis, lymphoid hyperplasia, and severe hemosiderosis in an accessory spleen. The only consistent change in the intact animals was splenomegaly.     

高致病性猪繁殖与呼吸综合征病毒对4月龄莱芜黑猪的致病性分析

本试验旨在探讨高致病性猪繁殖与呼吸综合征病毒(HP-PRRSV)对地方品种猪的致病特点。将HP-PRRSV经滴鼻感染4月龄健康莱芜黑猪,观察接毒后的表现,于接毒不同时期颈静脉采血,ELISA试剂盒(IDEXX)检测外周血血清抗体水平的动态变化,定期剖杀,采集相关的器官组织制备组织切片,HE染色,观察不同组织的动态病理学变化,免疫组化染色检测病原在不同组织中的分布。结果表明,攻毒后第2天便出现一定的临床症状,但持续2d后症状就基本消失,感染猪未见死亡。攻毒后5d便可检测到抗体阳性(1/7),14d抗体达峰值。攻毒后3d便可见间质性肺炎,轻微的病毒性脑炎,实质器官颗粒变性;攻毒后7d出现典型的间质性肺炎、淋巴组织坏死、各段肠管大量嗜酸性粒细胞浸润及实质器官出现空泡变性。在攻毒后2～4周内,肺一直表现典型的间质性肺炎,病毒性脑炎逐渐加重,肾上腺变性坏死,胰腺轻微的炎性细胞浸润,甲状腺轻微充血、出血,实质器官出现严重的空泡变性。PRRSV抗原阳性信号出现在淋巴组织(淋巴结、脾、扁桃体)、气管、心、肝、肺、肾、胃、十二指肠、空肠、回肠、甲状腺、肾上腺、颌下腺、子宫、大脑及小脑内;盲肠、结肠、直肠、膀胱、胰腺、输卵管及卵巢均未见到阳性信号。阳性信号主要位于感染细胞的胞质中,偶尔出现在核内。试验结果表明:HP-PRRSV人工感染4月龄莱芜黑猪具有广泛的组织嗜性,并导致广泛的组织损伤,但临床症状表现轻微,未见死亡现象,4月龄莱芜黑猪对HP-PRRSV感染具有较强的抵抗力。试验结果为进一步研究HP-PRRSV对我国地方猪与外源品种猪的致病性差异提供了一定的理论依据。     

Bluetongue virus-induced hydranencephaly in cattle

Direct inoculation of bluetongue virus into 125-day bovine fetuses resulted in development of hydranencephaly. The earliest lesions after virus inoculation were a severe necrotizing encephalitis, which was most prominent in the cerebrum, and an associated nonsuppurative meningitis. At birth, the brains of infected fetuses had thin-walled cerebral hemispheres, dilated lateral ventricles, and cerebral cysts. No gross lesions were observed in the brain stem or cerebellum. Two morphologically different lesions were present in the brain of a fetus sacrificed 20 days after virus inoculation. There were discrete foci of hemorrhagic cerebral necrosis that resembled infarcts and widespread microcavitations of the intermediate and subventricular zones. Changes consistent with vascular damage were present in the brains of fetuses sacrificed 12 and 20 days after virus inoculation. Calves with bluetongue virus-induced hydranencephaly would have poor viability, but they would not be expected to have any significance as virus reservoirs.     

Experimentally induced ostertagiosis in rabbits inoculated with Ostertagia ostertagi of bovine origin

Weanling specific-pathogen-free rabbits were orally inoculated with 50,000 Ostertagia ostertagi 3rd-stage infective larvae cultured from bovine feces and were killed 42 days after inoculation. Two preliminary trials were done, using conventionally reared weanling rabbits inoculated with 2,500, 5,000, and 50,000 O ostertagi 3rd-stage larvae and dexamathasone in 1 of the trials; the rabbits were killed 14 and 28 days after inoculation. Fecal egg counts were monitored, and worm burdens were determined. The pH of the gastric contents was measured at necropsy. Recoveries of the parasite from the gastric mucosa comprised early 4th-stage larvae and larvae that had developed beyond the early 4th stage. The maximum worm burden established at 42 days after inoculation was 1,668 immature nematodes or 3.34% of the inoculum. Gross and microscopic gastric lesions were present. Gross nodular mucosal elevations, which tended to be confluent in the cardiac region, were observed. Microscopic changes were principally mucosal hyperplasia, focal lymphocyte accumulation with moderate glandular dilation, and slight variable eosinophil and plasma cell accumulation. The pathologic changes had characteristics similar to those in cattle infected with O ostertagi and other conditions characterized by gastric mucosal hyperplasia.     

Bovine mycoplasma mastitis from intramammary inoculation of small numbers of Mycoplasma bovis. I. Microbiology and pathology

Intrammary inoculation of 70 colony forming units (cfu) of Mycoplasma bovis into one quarter of four previously non-infected cows resulted in severe mastitis in inoculated and uninoculated quarters. Hematogenous spread of the infection was most likely, as mycoplasma was isolated from the peripheral blood of three of four cows and the milking machine was designed to prevent quarter to quarter communication of milk and air. The presence of large numbers of mycoplasma exceeding 10⁶ cfu/ml of milk preceded the onset of overt sero-purulent mastitis by 1–3 days. In general, the severity, duration of the infection and within cow spread of mastitis to adjacent quarters after the inoculation of 70 cfu was indistinguishable from naturally occurring mycoplasma mastitis.The pathology of the chronically infected quarters consisted of alveolar involution and moderate to severe mononuclear infiltration and an increase in interalveolar and loose connective tissue. The quarters of one cow resolving the infections at the time of slaughter were not as severely affected and contained numerous milk-producing alveoli and many alveoli with hyperplasia of the alveolar cells.     

Experimental microcyst sarcocystis infection in lambs: pathology

Six 34- to 42-day-old lambs raised in coccidia-free conditions were inoculated with 70,000 sporocysts derived from sheep heart with microscopic sarcocysts. Fever and mild anorexia occurred between 25 and 33 days after inoculation. A transient anaemia was most marked 32 days after inoculation. Lambs were killed and examined 14, 25, 33, 42, 60 and 81 days after inoculation. Gross lesions were absent. First and second generation meronts were present in endothelial cells at 25 and 33 days after inoculation. Meronts were most numerous in kidney glomeruli. Developing sarcocysts were rare at 42 days after inoculation. Sarcocysts with a primary cyst wall 2 to 3 micron thick composed of palisade projections were common at 60 and 81 days after inoculation in striated muscle and brain. Mild to severe striated muscle myositis and non-suppurative encephalitis or encephalomyelitis with glial nodules were observed 25 to 81 days after inoculation. Sarcocyst frequency varied considerably; it was highest in myocardium, M vastus intermedius, M vastus medialis, M extensor carpi radialis and tongue muscle and was lowest in M masseter.     

An outbreak of congenital hydranencephaly and cerebellar hypoplasia among calves in South Kyushu, Japan: a pathological study

An outbreak of congenital hydranencephaly and cerebellar hypoplasia occurred between November 1985 and May 1986 in Miyazaki, South Kyushu, Japan. Seventy-three calves had nervous signs of varying severity such as inability to stand, locomotor difficulties, defective vision and difficulty in sucking. At necropsy, 62 calves had macroscopic lesions in the central nervous system: hydranencephaly accompanied by cerebellar hypoplasia in 47; hydranencephaly alone in eight; and dilatation of the lateral ventricle in seven; none had arthrogryposis. Microscopically, all 62 cases involved various degrees of hypoplasia of neural components, such as total or partial thinning of the cerebral or cerebellar laminae. Heterotopia, such as abnormal islands of granule cells or Purkinje cells was also observed. Fourteen of these animals had other lesions such as non-purulent encephalitis, focal gliosis, neuronal degeneration, calcification or pseudocalcification, and cholesterol deposits, activation of vascular endothelial cells and haemorrhage. From the findings, these cases were considered to represent mainly hypoplasia of nerve tissue due to infection with a virus different from Akabane virus.     

Effects of cyclophosphamide in newly hatched chickens after inoculation with avian nephritis virus

Effects of immunosuppression were compared in newly hatched chickens given cyclophosphamide (CY) after inoculation with avian nephritis virus (ANV). All CY-treated infected chickens died within 13 days after inoculation of the virus and had heavy urate deposits throughout the body. However, non-CY-treated infected, CY-treated noninfected, and non-CY-treated noninfected control chickens survived through the observation period. In a chronologic study, the value of serum uric acid in CY-treated infected chickens was more than 3 times higher than that in non-CY-treated infected chickens, and more than 9 times higher than in noninfected chickens. Serum uric acid values were coincident with the positive degree of ANV antigen in the tubular epithelial cells in the kidneys and with the severity of renal degeneration. Serologic and immunohistologic examinations did not reveal detectable antibody and IgG- and IgM-containing cells in the spleen and kidneys of CY-treated infected chickens. However, non-CY-treated infected chickens had an increased number of IgM- and IgG-containing cells and antibody against ANV on postinoculation day 6. These findings demonstrated that CY treatment enhanced the susceptibility of chickens to ANV infection.     

Ovine listerial encephalitis: analysis, hypothesis and synthesis

Analysis of field data suggested that listerial encephalitis in sheep was most common in winter and early spring in the age groups of sheep which would be cutting, changing and possibly losing teeth. It was hypothesised that under these conditions ingested Listeria monocytogenes could reach the fine dental terminals of the trigeminal nerve causing an ascending neuritis and encephalitis. Experimental inoculation of organisms into the dental pulp demonstrated the feasibility of this route of infection. Histological encephalitis was evident six days after inoculation but the incubation period to clinical neurological disease was at least three weeks.     

Age-related lesions in laboratory-confined raccoons (Procyon lotor) inoculated with the agent of chronic wasting disease of mule deer.

This communication documents age-associated pathologic changes and final observations on experimental transmission of chronic wasting disease (CWD) by the intracerebral route to raccoons (Procyon lotor). Four kits were inoculated intracerebrally with a brain suspension from mule deer with CWD. Two uninoculated kits served as controls. One CWD-inoculated raccoon was humanely killed at 38 months after inoculation, and 1 control animal died at 68 months after inoculation. Both animals had lesions that were unrelated to transmissible spongiform encephalopathy. Six years after inoculation, none of the 3 remaining CWD-inoculated raccoons had shown clinical signs of neurologic disorder, and the experiment was terminated. Spongiform encephalopathy was not observed by light microscopy, and the presence of abnormal prion protein (PrP(d)) was not detected by either immunohistochemistry or Western blot techniques. Age-related lesions observed in these raccoons included islet-cell pancreatic amyloidosis (5/6), cystic endometrial hyperplasia (3/4), cerebrovascular mineralization (5/6), neuroaxonal degeneration (3/6), transitional-cell adenoma of the urinary bladder (1/6), and myocardial inclusions (4/6). The latter 2 pathologic conditions were not previously reported in raccoons.     

鸭肝炎鸡胚化弱毒MY人工接种雏鸭后组织结构动态变化比较研究

对鸭肝炎鸡胚化弱毒株MY接种4日龄雏鸭后的组织变化进行了动态观察比较研究。结果显示：雏鸭接毒12 h肝、肾呈现轻度细胞变性;48 h后组织变性程度减轻,汇管区周围细胞增生;144 h细胞核、浆染色加深,组织修复迹象明显;14 d结构正常。接毒12 h脾脏白髓、法氏囊滤泡中淋巴细胞减少,72 h脾、24 h法氏囊中淋巴细胞有所增多。心脏、肺、脑组织在接毒各期皆有轻度的充血、出血。鸭肝炎鸡胚化弱毒株MY与标准毒导致的多组织变性、坏死相比,其变性轻而可逆;与疫苗HY所致的组织变化相似,但结构恢复时间早。结果表明：鸭肝炎鸡胚化弱毒株MY接种4日龄雏鸭,虽可造成雏鸭肝、肾等实质器官轻微的组织病变,但损伤的组织结构可在短期内修复,并恢复至正常;脾脏、法氏囊中的淋巴细胞在接毒后,也由减少到增多。本研究为鸭肝炎鸡胚化弱毒株MY用作鸭肝炎疫苗株的安全性从病理组织学角度提供了依据。     

Induced transplacental transmission of Neospora caninum in cattle.

Three Jersey cows were inoculated SC and IM with 26 million Neospora caninum tachyzoites at 129 (cow 1), 126 (cow 2), and 81 (cow 3) days after mating. Cows remained clinically normal for at least 1 month after inoculation of N caninum. Cow 1 was euthanatized 32 days after inoculation because of gangrenous mastitis. Cow 1 had a live fetus with no gross lesions; however, microscopic lesions were seen in the fetus and consisted of severe nonsuppurative necrotizing encephalitis of the cerebral white matter. Neospora caninum was identified in lesions by staining with anti-N caninum serum in an immunohistochemical test, by bioassays in mice, and by inoculation of bovine monocyte cultures with fetal tissue homogenate. Neither N caninum nor lesions were associated with infection with the protozoon identified in tissues of cow 1. Cows 2 and 3 aborted small autolysed fetuses 101 and 74 days, respectively, after inoculation with N caninum; the fetuses and attached placenta were unsuitable for laboratory investigations. Cows 2 and 3 remained clinically normal 4 months after abortion. Results of this study indicated that N caninum can be transmitted transplacentally in cattle.     

Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters.

The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice (n = 24, 6 to 8 weeks old) and hamsters (n = 9, 90-110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extraneural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extraneural disease before major central nervous system disease developed.     

Pathogenesis of Brucella abortus in chicken embryos

Chicken embryos inoculated with Brucella abortus at 6, 10, and 12 days of incubation were examined by light and electron microscopy. B. abortus was identified by avidin-biotin immunoperoxidase and immunogold techniques. Death occurred from 2 to 5 days post-inoculation, depending on age of the embryo and route of inoculation. B. abortus was recovered from all infected eggs. Brucellae had spread throughout all tissues and localized preferentially within cells of mesodermal derivation. Organ distribution and degree of bacterial replication varied with age of the embryo at time of inoculation. In 6-day-old embryos, B. abortus localized preferentially in endoderm and mesoderm of yolk sac wall, extra- and intraembryonic serosal epithelia, and glomeruli of the mesonephros. In 10- and 12-day-old embryos, B. abortus spread to all tissues; renal glomeruli, liver, spleen, and heart were most severely infected. Intracellular B. abortus was within the rough endoplasmic reticulum of mesenchymal, mesothelial, yolk endodermal, and hepatic cells. In mononuclear phagocytes, endothelial cells, and granulocytes, bacteria were within membrane-bound vacuoles. Intracellular replication of B. abortus in embryonic tissues, especially yolk endoderm, closely resembled that in experimental infections of trophoblasts.     

Ultrastructural Observation of Nasal and Pulmonary Intracellular Pasteurella multocida A:3 in Rabbits

Sixteen 8- to 9-week-old Pasteurella multocida-free rabbits were divided into two equal groups. Eight rabbits in one group were inoculated intranasally with P. multocida type A:3. The other eight were inoculated intranasally with phosphate-buffered saline and used as controls. Nasal swabs taken before and after inoculation were cultured for bacterial isolation. Post-mortem nasal swabs and lung samples were cultured for bacteriological isolation. Nasal mucosa and lung samples were collected and processed for transmission electron microscopy. Pasteurella multocida was isolated from the nasal cavity of all infected rabbits and from the lungs of four infected rabbits. Degenerative ultrastructural changes in epithelial cells and endothelial cells were seen in the infected rabbits. Deciliation of the cilated epithelium and hyperplasia of the goblet cells in the nasal mucosa were noted. Thickening of the alveolar septa due to hyperplasia of type II pneumocytes, swelling of the endothelial lining of capillaries and infiltration of inflammatory cells were also observed. Intracellular invasion of the nasal epithelial cells and of type II pneumocytes by the organism was observed. Coccobacilli were observed in membrane-bound vacuoles in the cytoplasm of these cells. The vacuoles were adjacent to the host-cell mitochondria and some of these vacuoles appeared to be fused to the mitochondrial membrane. Some type I pneumocytes with intracellular membrane-bound vacuoles containing bacterial cells showed protrusions, which appeared to detach into the alveolar lumina. These results indicated that P. multocida serotype A:3 in rabbits can invade the epithelial cell and cause structural changes in the interstitium, epithelium and endothelium. Heterophils and macrophages appear to play important roles in tissue injury.     

The pathogenesis of vesicular exanthema of swine virus and San Miguel sea lion virus in swine

Vesicular exanthema of swine virus type A48 or San Miguel sea lion virus type 2, when inoculated intradermally into swine, resulted in fluid-filled vesicles at the sites of inoculation in the snout, coronary band, and tongue. Pigs that developed vesicles also had fevers. Secondary vesicle formation varied, depending on virus serotype. Viremia was found in one pig infected with San Miguel sea lion virus five days after infection. Virus was recovered from nasal-oral passages for up to five days after infection in both groups of pigs and from the gastrointestinal and urinary tracts of pigs infected with San Miguel sea lion virus. Neutralizing antibodies began to increase three days after inoculation and reached peak titers in seven to ten days. In the absence of secondary bacterial infection, healing was well advanced by ten days after inoculation. Lesions usually were limited to nonhaired portions of the integument and tongue. Individual epithelial cells became infected when a break in the skin allowed virus access to susceptible epithelial cells from either exogenous or endogenous sources. Individual infected cells ruptured and adjacent cells were infected, resulting in the formation of multiple microvesicles. Centrifugal coalescence of microvesicles led to formation of grossly visible macrovesicles. Lesions rarely developed from viral contamination of intact hair follicles. A mild virus-induced encephalitis was seen in pigs infected with vesicular exanthema of swine virus, and virus was recovered from brain tissue of pigs infected with San Miguel sea lion virus.     

Vascular ultrastructure and DNA fragmentation in swine infected with Shiga toxin-producing Escherichia coli

Shiga toxins (Stx) produced by Escherichia coli cause systemic vascular damage that manifests as edema disease in swine and hemolytic uremic syndrome in humans. In vitro, Stx inhibit protein synthesis and, depending on circumstances, induce necrosis, apoptosis, or both. The mechanism of in vivo Stx-mediated vascular damage is not known. The ability of Stx to cause apoptosis of vasculature in vivo was studied in pigs with edema disease that was produced by oral inoculation with Stx-producing E. coli. Arterioles of ileum and brain were evaluated by terminal dUTP nick-end labeling (TUNEL) assay for DNA fragmentation in myocytes (10 infected pigs, 5 control pigs) and by transmission electron microscopy for ultrastructural changes characteristic of apoptosis (17 infected pigs, 8 control pigs). In comparison with controls, increased numbers of TUNEL-positive arterioles were detected in 6/10 (60%) subclinically affected pigs 14-15 days after inoculation. Ultrastructurally, lesions in myocytes consisted of lysis (necrosis), with cytoplasmic debris and nuclear fragments contained between intact basement membranes. Endothelial cell changes ranged from acute swelling to necrosis and detachment from basement membrane. Subclinically affected pigs (n = 14) tended to have changes predominantly in myocytes, whereas pigs with clinical illness (n = 3) more commonly had changes in endothelial cells. The arteriolar lesions and clinical signs of edema disease are attributed to the effects of Stx on vasculature. Therefore, our findings suggest that the Stx-induced arteriolar lesions seen in this study were primarily necrotic, not apoptotic. We suspect that necrosis was the principal cause of the DNA fragmentation detected.     

Effects of oral administration of tilmicosin on pulmonary inflammation in piglets experimentally infected with Actinobacillus pleuropneumoniae

OBJECTIVES: To determine the effects of oral administration of tilmicosin in piglets experimentally infected with Actinobacillus pleuropneumoniae. ANIMALS: Forty 3-week-old specific-pathogen free piglets. PROCEDURES: Piglets were assigned to 1 of 4 groups as follows: 1) uninfected sham-treated control piglets; 2) infected untreated piglets that were intratracheally inoculated with 10(7) CFUs of A pleuropneumoniae; 3) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received tilmicosin in feed (400 ppm [microg/g]) for 7 days prior to inoculation; or 4) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received chlortetracycline (CTC) in feed (1100 ppm [microg/gl) for 7 days prior to inoculation. Bronchoalveolar lavage (BAL) fluid and lung tissue specimens of piglets for each group were evaluated at 3 or 24 hours after inoculation. For each time point, 4 to 6 piglets/group were studied. RESULTS: Feeding of CTC and tilmicosin decreased bacterial load in lungs of infected piglets. Tilmicosin delivered in feed, but not CTC, enhanced apoptosis in porcine BAL fluid leukocytes. This was associated with a decrease in LTB4 concentrations in BAL fluid of tilmicosin-treated piglets, compared with untreated and CTC-treated piglets, and also with a significant decrease in the number of pulmonary lesions. Tilmicosin inhibited infection-induced increases in rectal temperatures, as measured in untreated and CTC-treated piglets. Pulmonary neutrophil infiltration and prostaglandin E2 concentrations in the BAL fluid were not significantly different among groups at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of tilmicosin to infected piglets induces apoptosis in BAL fluid leukocytes and decreases BAL fluid LTB4 concentrations and inflammatory lung lesions.