Fever In Rabbits Research Articles

Evaluation of antipyretic activity of Belladonna and Pyrogenium ultrahigh dilutions in induced fever model.

Background Belladonna and Pyrogenium are commonly used to treat fever in homeopathy. But in vivo antipyretic activity of these medicines is not reported yet. The study was conducted to evaluate the effectiveness of ultrahigh dilutions of Belladonna (Bell) and Pyrogenium (Pyro) in fever model of rabbits induced by Baker's yeast. Methods Healthy, local strain rabbits (♂ and ♀) were divided into seven groups (n=42): Normal control, negative control, standard control, pyro 1000c, pyro 200c, Bell 1000c and Bell 200c. Fever was induced by intra peritoneal injection of 135 mg/kg Baker's yeast suspension. Rectal temperature was measured hourly. All the medicines were administered once a day. The results were expressed as mean ± SEM. ANOVA and least significant difference post hoc test were applied for checking the level of significance, p-value of ≤0.05 was considered significant statistically. Results Pyro in both potencies significantly reduced fever in rabbits compared to negative control group, while both potencies of Bell were ineffective. Paracetamol and Pyro 1000c reduced by 1.2 °C (39.7 ± 0.1 to 38.5 ± 0.1), while Pyro 200c reduced by 1 °C temperature (39.7 ± 0.5 to 38.7 ± 0.2). Conclusions Pyro possesses marked antipyretic activity in rabbit's Baker's yeast fever model. It would embolden its clinical use in fever with more guarantee of its efficacy. However, caveat of small sample size necessitates replication of experiment in large sample size.

Tularemia in Germany-A Re-emerging Zoonosis.

Tularemia, also known as “rabbit fever,” is a zoonosis caused by the facultative intracellular, gram-negative bacterium Francisella tularensis. Infection occurs through contact with infected animals (often hares), arthropod vectors (such as ticks or deer flies), inhalation of contaminated dust or through contaminated food and water. In this review, we would like to provide an overview of the current epidemiological situation in Germany using published studies and case reports, an analysis of recent surveillance data and our own experience from the laboratory diagnostics, and investigation of cases. While in Germany tularemia is a rarely reported disease, there is evidence of recent re-emergence. We also describe some peculiarities that were observed in Germany, such as a broad genetic diversity, and a recently discovered new genus of Francisella and protracted or severe clinical courses of infections with the subspecies holarctica. Because tularemia is a zoonosis, we also touch upon the situation in the animal reservoir and one-health aspects of this disease. Apparently, many pieces of the puzzle need to be found and put into place before the complex interaction between wildlife, the environment and humans are fully understood. Funding for investigations into rare diseases is scarce. Therefore, combining efforts in several countries in the framework of international projects may be necessary to advance further our understanding of this serious but also scientifically interesting disease.

Evaluation of antipyretic activity of hydroalcoholic extract of Corchorus depressus Linn. in Escherichia coli–induced pyretic rabbits

This study was conducted to investigate the antipyretic effect of the hydroalcoholic extract of Corchorus depressus Linn. against Escherichia coli ( E. coli)-induced pyrexia in rabbits. Hydroalcohalic extracts of C. depressus were given orally at 25, 50, and 100 mg/kg for antipyretic affect in E. coli-induced fever in rabbits. The animals were divided into five groups of five each. Among these five groups, three received various doses of experimental treatments, whereas the fourth one served as positive control and received paracetamol. The fifth group of animals served as negative control and received no treatment. The body temperature of the rabbits was measured rectally over a period of 5 h. C. depressus exhibited better effects at dose rate of 25, 50, and 100 mg/kg. The hydroalcoholic extract of C. depressus has significant antipyretic effect. These results lend support to the popular use of C. depressus in traditional medicine as a remedy for pyrexia and suggest that the characterization of the principles for such activity deserves further investigation.

Continuous Passaging of a Recombinant C-Strain Virus in PK-15 Cells Selects Culture-Adapted Variants that Showed Enhanced Replication but Failed to Induce Fever in Rabbits.

Classical swine fever virus (CSFV) is the etiologic agent of classical swine fever, a highly contagious disease that causes significant economic losses to the swine industry. The lapinized C-strain, a widely used vaccine strain against CSFV, has low growth efficiency in cell culture, which limits the productivity in the vaccine industry. In this study, a recombinant virus derived from C-strain was constructed and subjected to continuous passaging in PK-15 cells with the goal of acquiring a high progeny virus yield. A cell-adapted virus variant, RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC variants indicated that at least six nucleotide changes were fixed in RecCpp80. Further adaption of RecCpp80 variant in swine testicle cells led to a higher virus yield without additional mutations. Introduction of each of these residues into the wild-type RecC backbone showed that one mutation, M979R (T3310G), located in the C-terminal region of E2 might be closely related to the cell-adapted phenotype. Rabbit inoculation revealed that RecCpp80+10 failed to induce fever in rabbits, whereas RecCpp40+10 caused a fever response similar to the commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell culture by introducing specific mutations in its E2 protein. The mutations in RecCpp80 that led to the loss of fever response in rabbits require further investigation. Continuous passaging of the C-strain-based recombinant viruses in PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at 3310 and 3531 might play major roles in the enhanced capacity of general virus reproduction. Such findings may help design a modified C-strain for improved productivity of commercial vaccines at reduced production cost.

Preliminary phytochemical analysis and in vivo evaluation of antipyretic effects of hydro-methanolic extract of Cleome scaposa leaves

Cleome scaposa has been associated with the prevention of many diseases as fever, abdominal complaints and cancer. But its antipyretic effect is not reported so far. The aim of this study was to assess the efficacy of C. scaposa in reducing temperature in Baker's yeast-induced fever model of rabbits. Rabbits were randomized into 4 groups (n = 24). Fever was induced in by Saccharomyces cerevisae (3 mL/kg of 10% suspension subcutaneous) in all study groups. Afterward, group 1, 2, 3 and 4 were orally administered with paracetamol 150 mg/kg b. wt., distilled water, C. scaposa 250 and 500 mg/kg b. wt. respectively. 500 mg/kg dosage was selected after dose fixation study. The standard control was paracetamol. Rectal temperature was recorded with the help of a digital thermometer. ANOVA followed by post hoc test was applied for statistical analysis of results. Results of the study indicate that C. scaposa possesses antipyretic activity comparable to that of standard drug paracetamol as it exhibited comparable antipyretic potential against baker's yeast-induced fever in rabbits. This study confirms the traditional use of C. scaposa in fever. So, it can be an alternative therapeutic choice in fever. However, specific constituents responsible for its antipyretic activity should be evaluated.

Effects of homoeopathic ultrahigh dilutions of Aconitum napellus on Baker's yeast-induced fever in rabbits

ObjectiveTo evaluate the effects of homoeopathic ultrahigh dilutions of Aconitum napellus in Baker's yeast-induced fever in rabbits. MethodsRabbits were divided into 4 groups and each group contained 6 rabbits. Baker's yeast suspension (20%) was injected subcutaneously. After fever induction, paracetamol and homoeopathic ultrahigh dilutions (A. napellus 200c and 1 000c) were given orally. Rectal temperature was measured with digital thermometer hourly. ResultsFever was induced in all the rabbits after 4 hours of Baker's yeast administration. A. napellus 200c and 1000c significantly reduced the temperature (P > 0.05). In positive control, temperature decrease was more significant (P > 0.001). ConclusionThe above findings indicate the effectiveness of ultrahigh dilutions of A. napellus in Baker's yeast-induced fever in rabbits. However, the effects were slower and less significant than standard medicine. Moreover, future research is required to know their mechanism of reducing temperature.

Role of Acupoint Area Collagen Fibers in Anti-Inflammation of Acupuncture Lifting and Thrusting Manipulation.

The role of the acupoint area collagen fibers in the efficacy of acupuncture lifting and thrusting (L&T) manipulation will be explored in this paper. 30 male NZW rabbits were randomly divided into 6 groups: sham operation group (Group N), model group (Group M), acupuncture without manipulation group (Group W), acupuncture L&T manipulation group (Group A), collagenase pretreatment group (Group JM), and collagenase pretreatment + acupuncture L&T manipulation group (Group JA). The bacterial endotoxin was used to generate the rabbit fever models. Acupuncture was applied at IL-11. The levels of IL-1β, TNF-α, and IL-4 and the rectal temperature were measured at 2 h, 4 h, and 6 h after modeling and the collagen fiber morphology at acupoint area was observed after 6 hours. Results. As compared with Group N, the levels of IL-1β and TNF-α in Group M were significantly higher; the level of IL-4 was significantly lower (P < 0.05). As compared with Group M, IL-1β and TNF-α in Groups W and A were significantly lower and IL-4 was significantly higher (P < 0.05). As compared with Group W, IL-1β and TNF-α in Group A were lower and IL-4 was higher (P < 0.05). The collagen fiber in Group A was slightly rough, distorted, and fractured. As shown in studies, the endotoxin-induced inflammatory response can be significantly inhibited by acupuncture whose efficacy can also be significantly improved by the manipulations. Collagenase pretreatment may be the first receptor to the mechanical force of the L&T manipulation.

Febrile temperature facilitates hERG/IKr degradation through an altered K+ dependence

Dysfunction of the rapidly activating delayed rectifier K(+) channel (IKr) encoded by the human ether-à-go-go-related gene (hERG) is the primary cause of acquired long QT syndrome (LQTS). Fever has been reported to trigger LQTS in various conditions. We aim to clarify the effect and underlying mechanisms of febrile temperature on hERG expressed in HEK cells, IKr in neonatal rat ventricular myocytes, and the QT interval in rabbits. Western blot analysis was used to determine the expression of hERG channel protein in stably transfected HEK 293 cells. Immunocytochemistry was used to visualize the localization of hERG channels. The whole-cell patch clamp technique was used to record hERG K(+) current (IhERG) in hERG expressing HEK 293 cells, as well as IKr, transient outward K(+) current (Ito), and L-type Ca(2+) current (ICa) in neonatal rat ventricular myocytes. Electrocardiographic recordings were performed in an in vivo rabbit model. Compared with culture at 37°C, culture at 40°C reduced the mature hERG expression and IhERG in an extracellular K(+) concentration-dependent manner. Point mutations that remove the K(+) dependence of hERG-S624T and F627Y-also abolished the febrile temperature-induced hERG reduction. In neonatal rat ventricular myocytes, febrile temperature prolonged the action potential duration and selectively reduced IKr in a manner similar to low K(+) culture. In an in vivo rabbit model, fever and hypokalemia synergistically prolonged the QT interval. Febrile temperature facilitates the development of LQTS by expediting hERG degradation through altered K(+) dependence.

Antibodies to ovine herpesvirus 2 glycoproteins decrease virus infectivity and prevent malignant catarrhal fever in rabbits

Ovine herpesvirus-2 (OvHV-2) is the etiological agent of sheep-associated malignant catarrhal fever (SA-MCF), a fatal lymphoproliferative disease of many species in the order Artiodactyla. Development of a vaccine is critical to prevent mortality. Because OvHV-2 has not been cultured in vitro, SA-MCF research is hindered by the lack of in vitro tools to study viral constituents and specific host immune responses. As an alternative, in this study the neutralizing activity of antibodies against OvHV-2 glycoproteins gB and gH/gL was evaluated in vivo using rabbits. OvHV-2-specific antibodies were developed in rabbits by immunization using biolistic delivery of plasmids expressing the genes of interest. A lethal dose of OvHV-2 was incubated with the antisera and then nebulized into rabbits. Virus neutralization was assessed by measuring infection parameters associated with the virus infectious dose. Anti-gB or anti-gH/gL antibodies alone blocked infection in five out of six rabbits (83%), while a combination of anti-gB and anti-gH/gL antibodies protected all six rabbits (100%) from infection. These results indicate that antibodies to OvHV-2 gB and gH/gL are capable of neutralizing virions, and consequently, reduce virus infectivity and prevent SA-MCF in rabbits. Thus, OvHV-2 gB and gH/gL are suitable targets to be tested in a SA-MCF vaccine aimed at stimulating neutralizing antibody responses.

Structure and Function of REP34 Implicates Carboxypeptidase Activity in Francisella tularensis Host Cell Invasion

Francisella tularensis is the etiological agent of tularemia, or rabbit fever. Although F. tularensis is a recognized biothreat agent with broad and expanding geographical range, its mechanism of infection and environmental persistence remain poorly understood. Previously, we identified seven F. tularensis proteins that induce a rapid encystment phenotype (REP) in the free-living amoeba, Acanthamoeba castellanii. Encystment is essential to the pathogen's long term intracellular survival in the amoeba. Here, we characterize the cellular and molecular function of REP34, a REP protein with a mass of 34 kDa. A REP34 knock-out strain of F. tularensis has a reduced ability to both induce encystment in A. castellanii and invade human macrophages. We determined the crystal structure of REP34 to 2.05-Å resolution and demonstrate robust carboxypeptidase B-like activity for the enzyme. REP34 is a zinc-containing monomeric protein with close structural homology to the metallocarboxypeptidase family of peptidases. REP34 possesses a novel topology and substrate binding pocket that deviates from the canonical funnelin structure of carboxypeptidases, putatively resulting in a catalytic role for a conserved tyrosine and distinct S1' recognition site. Taken together, these results identify REP34 as an active carboxypeptidase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells.

Development of an immunosensor for the detection of Francisella tularensis antibodies.

Tularemia, also known as rabbit fever, is a highly infectious zoonotic disease caused by a non-motile and non-spore-forming Gram-negative coccoid rod bacterium, Francisella tularensis. It occurs naturally in lagomorphs (rabbits and hares), but many animals have been reported to be susceptible. Transmission to humans is mostly caused by inhalation of aerosolised bacteria, handling of infected animals, arthropod stings, and ingestion of contaminated foods and water. At present, pathogenic isolation, molecular detection, and serology are the most commonly used methods to confirm the diagnosis of tularemia. In this work, an electrochemical immunosensor for the detection of anti-F. tularensis antibodies was developed, consisting of gold-based self-assembled monolayers of a carboxylic-group-terminated bipodal alkanethiol that is covalently linked to a lipopolysaccharide (LPS) that can be found in the outer membrane of the bacteria F. tularensis. The presence of anti-F. tularensis antibodies was measured using horseradish peroxidase-labelled protein A (HRP-protein A) from Staphylococcus aureus, and the developed immunosensor gave a stable quantitative response to different anti-F. tularensis FB11 antibody concentrations after 30 min with a limit of detection of 15 ng/mL, RSD of 9%, n = 3. The developed immunosensor was tested with serum from animals infected with tularemia and was compared to the results obtained using ELISA showing an excellent degree of correlation.

Synthesis and biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory, analgesic and antipyretic agent

A series of schiff base derivatives of 4-aminophenazone (4APZ-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one) with different aldehydes were synthesized. The synthetic compounds were screened for their anti-inflammatory, analgesic and antipyretic activities. The characterization of synthesized compounds was carried out by 1H NMR, 13C NMR and MS. Carrageenan-induced paw oedema (CIPO) and histamine induced paw oedema (HIPO) methods were used to determine the anti-inflammatory activity of commercial sample of 4APZ and its synthesized schiff bases in mice. The anti-inflammatory activity was in the order of 4APZAB>4APZBB>4APZCB>4APZVn and all the test compounds exhibited considerable dose dependent inhibition of the paw oedema. The effect of the compounds on membrane stabilization was also determined which showed that compounds 4APZ (120 and 240mg/kg doses), 4APZAB (160mg/kg) and 4APZVn (600mg/kg) produced highly significant inhibition (P<0.001) of hypotonicity-induced haemolysis. Further, it was also observed that 4APZ (120 and 240mg/kg doses), 4APZBB (500mg/kg) and APZCB (150, 300 and 600mg/kg dose) produced highly significant inhibition (P<0.001) of albumin denaturation; a consistent dose dependent anti-inflammatory effect of test compounds as compared to the standard drug. Analgesic activity of the compounds was investigated by formalin-induced paw licking (FIPL) and acetic acid-induced writhing (AIW) methods in mice. It was observed that 4APZ (240mg/kg), 4APZAB (160mg/kg), 4APZBB (500mg/kg), 4APZCB (600mg/kg) and 4APZVn (600mg/kg) showed analgesic effect with highly significant (P<0.001) reduction of paw licking and writhing activity in the treated mice. The order of analgesic effect of the compounds was 4APZAB>4APZBB>4APZVn>4APZCB. Moreover, phenobarbitone-induced sleeping time (PIST) in mice was also studied but only 600mg/kg of 4APZVn significantly increased the duration of induced sleep which also suggested its sedative property. Brewer’s yeast was used to induce fever in rabbits and analysed the compounds for their antipyretic activity. Different doses of 4APZ for different time durations (240mg/kg-after 1h, 120 and 240mg/kg doses-after 2h) produced highly significant (P<0.001) inhibition of hyperpyrexia. Other compounds showed good antipyretic activity after 2, 3 and 4h.

Structure and Function of Two Putative Virulence Factors from Francisella Tularensis

F. tularensis is a poorly understood category A priority pathogen and the etiological agent of Tularemia, or rabbit fever. Previous work by coworkers at LLNL identified seven putative virulence factor proteins, for which most have weak homology to proteins of known function. These seven proteins presumably are secreted host effector proteins, as they are important for inducing an encysted morphology in F. tularensis infected amoeba. Subsequent genetic studies have further implicated some of these ORFs as having a role in infection of human cells in culture. We have applied a structural-functional genomics approach in an attempt to elucidate the function of these rapid encystment proteins (REPs). Here we present the crystal structures of REP24 (24 kD) and REP34 (34 kD) and report on their putative function. REP24 appears to be a cysteine protease with a novel arrangement of the active-site catalytic triad, and we show that it binds to the cysteine protease inhibitor, JPM-565, both in vitro and in crystallo. REP34 By structural homology and, REP34 appears to be a Zn-dependent carboxypeptidase that possesses a novel fold that deviates from related funnelins, resulting in a rearranged active and substrate-recognition sites. We show the definitive presence of a Zn by anomalous diffraction, and catalytic activity of the enzyme using hippuryl-L-Arg. We believe that these structures provide potential starting points for rational design of new therapeutics against tularemia and, combined with further biochemical evidence, will provide important insights into the molecular mechanisms of F. tularensis infection.

Novel inhibitors of acetate kinase from Francisella tularensis

Developed as a bioweapon in the 1940's, Francisella tularensis is the pathogenic bacteria responsible for tularemia, or rabbit fever. In order to develop new treatments for weaponized strains of F. tularensis, potential inhibitors F. tularensis acetate kinase were identified in silico and experimentally tested. Often kinase activity is probed using relatively expensive NADH‐linked assays. Here, we utilized an inexpensive kinetic assay that monitors the production of acetyl phosphate via reaction with hydroxylamine to rapidly characterize potential inhibitors of F. tularensis acetate kinase. The KM values for ATP and acetate were determined to be 1.4 and 15.4 mM, respectively, and the Vmax was determined to be 40.6 μmol min−1 mg−1. Computational screening using DOCK allowed the identification of potential inhibitors from the National Cancer Institute's Developmental Therapeutics Program. Ten compounds were obtained and tested, and two of these reduce the activity of F. tularensis acetate kinase significantly, though at relatively high concentrations. Using these structures as lead compounds, we are mining the database for similar compounds to test as inhibitors. This research was funded by the Wabash College Haines Biochemistry Fund.

Characteristics of Tularemia in Kosovo 2010

Beckground: Francisella tularensis is a gram-negative zoonotic pathogen primarily of animals and occasionally of humans. The disease is now recognized as tularemia in most parts of the world, but it has been called rabbit fever, deer-fly fever, and market men’s disease in the United States; wild hare disease (yato-byo) and Ohara’s disease in Japan; and water-rat trappers’ disease in Russia. Tularemia continues to be responsible for significant morbidity and mortality, despite the availability of numerous antibiotics active against the organism. The first cases of tularaemia in Kosovo are reported in the south-western part of Kosovo, in the region of Gjakova in April 2000 in the village of Brovina - 22 patients who were infected through contaminated well water. In the meantime disease is spread in villages of Skivjan, Korenica, Batusha and later throughout Kosovo.Aim: The aim of this study is presentation of characteristics of Tularemia in Kosovo in 2010 and analyzes of the epidemiological, clinical and treatment features of Tularaemia in Kosovo.Methods: We analyzed 53 cases of tularaemia (from 320 patients with tularaemia in Kosovo in 2010) that were from 12 municipalities of Kosovo. The largest number of patients were from Municipality of Vushtria (11 patients) and municipality of Skenderaj (9 patients). All these cases were from rural areas; this confirms that social and epidemiological conditions are very important for appearance of this disease. We have analyzed the data from their medical histories, which includes their medical anamnesis, clinical examination, laboratory tests and their treatment.Results: The mean age of patients was 22 years, 13 patients were children under the age of 10 years. Patients were hospitalized an average of 14.7 days, while incubation time of the disease was an averaging of 28 days. Social and epidemiologic conditions were important factors in the appearance of the disease; 29 patients were water supplied only from wells. All patients were from rural areas. Clinical manifestations were temperature, neck pain, neck and axillary lymphadenopathy, and apathy. Clinically, glandular form has dominated. From laboratory tests, 51 of patients had high erythrocyte sedimentation rate, 13 cases had a slight anemia, and 34 patients had leukocytosis. Other laboratory tests were in normal values. Agglutination test in all cases was positive. All cases were treated with antibiotics; 31 patient were treated with gentamicin, 8 patients were treated with streptomycin and 14 patient were treated with other antibiotic. Incision and drainage of the gland as adjuvant therapy was applied in 27 patient.Conclusions: In this late decade in our country, tularemia continues to be a disease that represents a healthcare problem. Glandular forms of tularemia dominate in Kosovo. Treatment with gentamicin has had good effects. Incision and drainage of the inflamed glands has shown to be a good method in accelerating the recovery of patient. Prophylaxis has to be applied for prevention of the disease.

Effects of diflunisal on fever in the rabbit and the rat.

The antipyretic efficacy of diflunisal was assessed in rats made febrile by yeast and in rabbits made febrile by bacterial endotoxin. Diflunisal was a more potent antipyretic than aspirin in rats, reducing a maximum fever in doses not producing overt toxic effects. In contrast, submaximal fever in rabbits was not reduced by diflunisal. Fatal hyperthermia of rapid onset was observed in rats and rabbits receiving high doses of diflunisal after administration of microbial pyrogen but not in control animals. These data indicate the toxicity of diflunisal may be potentiated by the presence of pyrogens. It is concluded that the apparent antipyretic efficacy of a drug can depend on the species-pyrogen combination used to screen for antipyresis.

AD-1590, a potent antagonist of lipopolysaccharide-induced fever in rabbits.

The antipyretic activity of AD-1590 (2-[8-methyl-10,11-0xodibenz[b,f]oxepin-2-yl]propionic acid), a non-steroidal anti-inflammatory drug with a novel chemical structure, was investigated in rabbits with lipopolysaccharide (LPS)-induced fever and monkeys with leucocytic pyrogen-induced fever. AD-1590 produced a dose-related inhibition of the LPS-fever at oral doses of 0.1 mg kg-1 or more (ED50 = 0.089 mgg kg-1). Its potency was 10-12, 20-35, 100-170, 400-540, greater than 1500 and greater than 2000 times that of ketoprofen, diclofenac sodium, indomethacin, ibuprofen, mefenamic acid and aspirin, respectively. The fever caused by leucocytic pyrogen was significantly inhibited by intravenous administration of 0.1-0.2 mg kg-1 of AD-1590 (10 mg kg-1 oral or i.v.) did not affect body temperature in afebrile rabbits or monkeys. These results suggest that AD-1590 shows a potent antipyretic activity in the rabbit and monkey and is a potent antagonist of LPS-fever.

Evidence against putrescine and polyamines as endogenous mediators of fever.

Endogenous concentrations of putrescine, spermidine, spermine and related biosynthetic enzymes were not affected by the administration of bacterial endotoxin and the subsequent development of fever in rabbits. In addition, the febrile response to endotoxin was unaffected either by the ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine or by putrescine. These data indicate polyamines are not involved in the development of fever.

Characterization of ovine herpesvirus 2-induced malignant catarrhal fever in rabbits

Malignant catarrhal fever (MCF) is a frequently fatal lymphoproliferative disease syndrome primarily of ruminant species, caused by gammaherpesviruses in the genus Macavirus. Ovine herpesvirus 2 (OvHV-2), carried by sheep, causes sheep-associated MCF worldwide, while Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest, causes wildebeest-associated MCF, mainly in Africa. Diseases in rabbits can be induced by both viruses, which are clinically and pathologically similar; however, recent studies revealed different expression of viral genes associated with latency or lytic replication during clinical disease between the two viruses. In this study, we further characterized experimentally induced MCF in rabbits by nebulization with OvHV-2 from sheep nasal secretions to elucidate the course of viral replication, along with in vivo incorporation of 5-Bromo-2′-Deoxyuridine (BrdU), to evaluate lymphoproliferation. All six rabbits nebulized with OvHV-2 developed MCF between 24 and 29 days post infection. OvHV-2 DNA levels in peripheral blood leukocytes (PBL) remained undetectable during the incubation period and increased dramatically a few days before onset of clinical signs. During the clinical stage, we found that predominantly lytic gene expression was detected in PBL and tissues, and both T and B cells were proliferating. The data showed that the viral gene expression profile and lymphoproliferation in rabbits with OvHV-2 induced MCF were different from that in rabbits with AlHV-1 induced MCF, suggesting that OvHV-2 and AlHV-1 may play a different role in MCF pathogenesis.

Central interleukin-10 attenuated lipopolysaccharide-induced changes in core temperature and hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2

It has been documented that intravenous lipopolysaccharide (LPS) in rabbits causes fever accompanied by increased levels of extracellular glutamate, hydroxyl radicals, and prostaglandin E2 (PGE2) in the hypothalamus and circulating tumor necrosis factor-alpha (TNF-α). This investigation was to determine whether central interleukin-10 (IL-10) exerted its antipyresis by reducing changes in circulating TNF-α and extracellular glutamate, hydroxyl radicals and PGE2 in the hypothalamus. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determinating extracellular glutamate, hydroxyl radicals, and PGE2 in situ. It was found that systemically injected LPS (2μg/kg, intravenously) increased the levels of core temperature, and extracellular glutamate, hydroxyl radicals, and PGE2 in the hypothalamus accompanied by increased plasma levels of TNF-α. Pretreatment with IL-10 (10–100ng, intracerebroventricularly) 1h before intravenous LPS significantly reduced the LPS-induced changes in extracellular glutamate, hydroxyl radicals, and PGE2 in the hypothalamus and fever, but not the increased levels of TNF-α in rabbits. These findings suggested that directly injected IL-10 into the lateral cerebral ventricle 1h before intravenous LPS exerted its antipyresis by inhibiting the changes in extracellular glutamate, hydroxyl radicals and PGE2 in the hypothalamus during LPS fever in rabbits.