Concanavalin-A as a Model for Induction of Murine Autoimmune Hepatitis: Role of TNF-α and NF-κß During The Acute Phase.

Autoimmune hepatitis (AIH) is a heterogeneous immune-mediated chronic liver disease affecting children and adults. It is important to rely on a specific animal model to study the hepatic changes and to evaluate the roles played by pro-inflammatory cytokines such as tumor necrosis factor alpha "TNF-α" and transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells "NF-κß" in the pathogenesis and outcome of the disease. This will help to identify specific targets for treatment of AIH. This study aimed at evaluating Concanavalin-A (Con A) as a model for induction of AIH and assessing splenocytes' TNF-α and hepatocytes' NF-κß levels at comparable durations after induction of hepatitis with Con A to evaluate the relationship between both factors. Materials and methods: A total of 130 outbreed CD1 mice were divided into group (1) which included 100 mice with induced AIH and group (2) included 30 normal mice as negative controls. Intra-peritoneal injection of Concanavalin-A was used to induce hepatitis. Hepatic injury was evaluated by the levels of liver enzymes, histopathological evidence for hepatic inflammatory infiltrate and/or apoptosis. Splenocytes and hepatocytes were cultured for assessment of TNF-α and NF-κß levels, respectively. Results: Con A injection caused a significant elevation in ALT and AST levels, portal inflammatory infiltrate, remarkable hepatocytes degeneration and marked increase of TNF-α levels, particularly within 24 hours, but all returned to normal within 1 week. Administration of another dose of Con A resulted in sharp significant elevation of liver enzymes, inflammatory infiltrate and hepatocyte apoptosis after 24 hours and sustained till the end of the study. There was a significant increase in NF-κß throughout most of the study duration following Con A injection as compared to that of normal mice. In conclusions, intra-peritoneal administration of Con A, particularly two doses, represents an efficient approach for induction of immune-mediated hepatitis. T-cells play a major role in AIH through release of TNF-α. Coincidently, hepatitis seems to be associated with elevation of NF-κß to protect hepatocytes. Thus TNF-α and NF-κß can represent targets for treatment of AIH either through inhibition or augmentation, respectively.

NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer Patients: Clinicopathological and Prognostic Significance.

Breast cancer is the most common gynecological malignancy in the world. In Egypt, it ranks the first among female malignancies with incidence of 37.7%. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to more individualized and optimized therapy. NY-BR-1 antigen has been shown to be frequently expressed in breast cancers. The study aimed to assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this antigen in Egyptian breast cancer females. The study was conducted on 60 females (10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer). NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag expression between benign and malignant breast cancer patients. There was a significant correlation between NY-BR-1 antigen expression and estrogen receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P = 0.032) among the studied individuals. In addition, there was a statistically significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast cancer group. It is correlated with tumor type (P < 0.001) and progesterone receptor status (P = 0.038). In conclusion, our work may represent a step towards identification of a new prognostic marker specific for breast cancer.

Effect of ultra violet irradiation on the interplay between Th1 and Th2 lymphocytes.

UNLABELLED: Although ultraviolet (UV) radiation is used to treat several types of diseases, including rickets, psoriasis, eczema, and jaundice, the prolonged exposure to its radiation may result in acute and chronic health effects particularly on the skin, eyes, and the immune system. AIM: This study was carried out to show the effect of UV on both of the lymphoproliferative response and their capacity to produce IL-12 and IL-10 in mice. METHODS: Mice were exposed to whole body UVB and tested for the effect of recovery times on lymphocyte proliferation and cytokine production. In addition, direct irradiation of spleens and lymphocyte suspension was carried out. Basal and mitogens-stimulated lymphocyte proliferation was assessed by MTT assay while IL-10 and IL-12 were measured using ELISA. RESULTS: There was a significant suppression in lymphocyte proliferation in comparison with control. IL-12 level was significantly reduced while the level of IL-10 was increased. Con A and PWM mitogens had no significant changes in IL-10 while Con A caused a highly significant increase in IL-12 at day 6 of recovery in UVB body irradiation. CONCLUSION: Exposure to UVB radiation could cause a state of immune suppression and shifts Th1/Th2 cell response. This effect is closely associated with the reduction of Th1 cytokines' expression and increase in Th2 cytokines' levels.

Effect of murine exposure to gamma rays on the interplay between Th1 and Th2 lymphocytes.

Gamma radiation radiotherapy is one of the widely used treatments for cancer. There is an accumulating evidence that adaptive immunity is significantly contributes to the efficacy of radiotherapy. This study is carried out to investigate the effect of gamma rays on the interplay between Th1/Th2 response, splenocyte lymphoproliferative response to polyclonal mitogenic activators and lymphocytic capacity to produce IL-12 and IL-10 in mice. Results showed that exposure of intact spleens to different doses of γ-rays (5, 10, 20 Gy) caused spontaneous and dose-dependent immune stimulation manifested by enhanced cell proliferation and elevated IL-12 production with decreased IL-10 release (i.e., Th1 bias). While exposure of splenocytes suspension to different doses of γ-rays (5, 10, 20 Gy) showed activation in splenocytes stimulated by PWM at 5 Gy then a state of conventional immune suppression that is characterized by being dose-dependent and is manifested by decreased cell proliferation and IL-12 release accompanied by increase in IL-10 production (i.e., Th2 bias). In addition, we investigated the exposure of whole murine bodies to different doses of γ-rays and found that the exposure to low dose γ-rays (0.2 Gy) caused a state of immune stimulation terminated by a remarkable tendency for immune suppression. Exposure to 5 or 10 Gy of γ-rays resulted in a state of immune stimulation (Th1 bias), but exposure to 20 Gy showed a standard state of immune suppression (Th2 bias). The results indicated that apparently we can control the immune response by controlling the dose of γ-rays.