Several studies have investigated allergic airway inflammation, a T helper 2 (Th2)-type immune response, using a mouse model of asthma. At present, however, no reports have described sex differences in the sensitivity of late airway inflammation (LAI). The LAI induced by ovalbumin in adult BALB/c mice was compared in males and females or sham-operated males and castrated males. The males showed less severe bronchial-bronchiolar inflammation with infiltration of eosinophils and lymphocytes and lower content of such cells in bronchoalveolar fluid than the females. Moreover, interleukin-4 (IL-4) mRNA expression levels in splenic cells were lower in the males than in the females. Castrated males performed like the females. Moreover, when compared with the sham-operated males, the castrated males showed lower testosterone levels in the blood. The present results suggest that less sensitivity for LAI in the males may be because of the decreased Th2 cell responses compared with the females. Moreover the testosterone, at least in part, may be responsible for the decreased Th2 cell responses in males in vivo.

In order to evaluate the involvement of c-yes and c-erbB-2 oncogene products, and p53 tumor suppressor protein in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 79 mammary tumors were analyzed immunohistochemically using antibodies against human c-yes p62 and c-erbB-2 products and p53. These 79 tumors were divided into 2 groups: 32 benign (2 adenosis, 7 simple adenomas, 14 complex adenomas, and 9 benign mixed mammary tumors) and 47 malignant tumors (26 simple adenocarcinomas, 7 complex adenocarcinomas, 5 solid carcinomas, 2 sclerosing carcinomas, 6 malignant mixed mammary tumors, and 1 malignant myoepithelioma). As a result of immunostaining, 40.6% (13/32) of the benign tumors and 21.3% (10/47) of the malignant tumors expressed the c-Yes oncogene product, ErbB-2 expression was detected in 50% (16/32) of the benign tumors and in 19.1% (9/47) of the malignant tumors. P53 expression was detected in 16% (4/25) of the benign tumors and in 30.6% (11/36) of the malignant tumors. Co-expression of c-Yes and ErbB-2, ErbB-2 and p53, and all 3 products was detected in 6, 1 and 7 tumors, respectively.

Mucus overproduction from goblet cells, a characteristic feature of the allergic asthmatic inflammation induced by ovalbumin (OVA) in mice, was examined morphologically. In OVA-untreated (normal) mice, there were no goblet cells in intrapulmonary bronchus and bronchiole. However, goblet cells with or without hyperplasia in the mucosa of inflamed bronchus-bronchiole were recognized in the allergic asthmatic mice. The non-ciliated epithelium containing electron lucent granules (mucus) showed many similarities to Clara cells, which have characteristic secretory granules and many mitochondria, except for the less-developed smooth endoplasmic reticulum seen in normal mice. Ciliated Clara cells with or without mucus were rarely recognized. In addition, mucus was found in neither ciliated nor basal epithelium. The present study suggests that goblet-cell metaplasia in the bronchus and bronchiole of inflamed mucosa may be derived, at least in part, from Clara cells.

Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which leads to pancreatic islet-cell destruction, resulting in a diabetes-like syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. The treatment of monoclonal antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5-9 days after infection) inhibited the development of insulitis and the elevation of blood glucose concentrations in a dose dependent manner. Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. These results suggest that Reo-2-triggered autoimmune insulitis may be mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation leading to islet cell destruction.

The usage of reovirus has reached phase II and III clinical trials in human cancers. However, this is the first study to report the oncolytic effects of reovirus in veterinary oncology, focusing on canine mast cell tumor (MCT), the most common cutaneous tumor in dogs. As human and canine cancers share many similarities, we hypothesized that the oncolytic effects of reovirus can be exploited in canine cancers. The objective of this study was to determine the oncolytic effects of reovirus in canine MCT in vitro, in vivo and ex vivo. We demonstrated that MCT cell lines were highly susceptible to reovirus as indicated by marked cell death, high production of progeny virus and virus replication. Reovirus induced apoptosis in the canine MCT cell lines with no correlation to their Ras activation status. In vivo studies were conducted using unilateral and bilateral subcutaneous MCT xenograft models with a single intratumoral reovirus treatment and apparent reduction of tumor mass was exhibited. Furthermore, cell death was induced by reovirus in primary canine MCT samples in vitro. However, canine and murine bone marrow-derived mast cells (BMCMC) were also susceptible to reovirus. The combination of these results supports the potential value of reovirus as a therapy in canine MCT but warrants further investigation on the determinants of reovirus susceptibility.

Sjögren's syndrome (SjS) is a chronic autoimmune disorder characterized by dry eyes and dry mouth due to dacryoadenitis and sialoadenitis with SS-A/Ro and/or SS-B/La autoantibodies in genetically predisposed individuals. Destruction of lacrimal and salivary glands by autoimmune reactions may lead to clinical manifestation. However, the mechanisms behind the decreased volume of secretions in tears and saliva are complex and are not fully understood. Exocrine gland dysfunction may precede autoimmunity (acquired immunity) or represent a process independent from inflammation in the pathogenesis of SjS. The preceded functional and morphologic changes of those tissues by nonimmunologic injury before the development of inflammation at the sites of target organs have been implicated. This paper focuses on the several factors and components relating to glandular dysfunction and morphologic changes by nonimmunologic injury during the preinflammatory phase in mouse model, including the factors which link between innate immunity and adaptive immunity.

The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of lupus nephritis during preactive phase (within seven months of age) in autoimmune lupus NZB x NZWF1 (B/WF1) mice was examined. Treatment of CpG-ODN was started at the age of 2.75 months and continued until 6.25 months. Overt disease began at the age of six months and progressed linearly at the age of 6.75 months in CpG-ODN-treated, but not control ODN-treated (control) groups. Also compared to control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis (GN), with prominent deposits of IgG2a and C3, which paralleled increased titre of IgG2a type anti-nuclear antibody in the blood. Among several cytokines (interleukin, IL-6, IL-4, IL-1alpha, IL-10, interferon-gamma and tumor necrosis factor-alpha) in blood, IL-6 production paralleled the development of lupus nephritis. The present study suggests that CpG-ODN may enhance IL-6 production. The role of IL-6 in the development of GN will be discussed.

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