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Acquired Immune Deficiency Syndrome (AIDS), a progressive immunodeficiency induced by Human Immunodeficiency Virus (HIV), frequently sets the stage for life-threatening tumors and opportunistic infections. The proposed study focuses on the immunological changes associated with HIV infection. Often superimposed diarrhea, causing malabsorption and malnutrition, leads to further immunosuppression and accelerated deterioration in many patients. The pathomechanism of Cryptosporidium-induced diarrhea is poorly understood and its relation to AIDS urgently requires investigation. We used LP-BM5 murine leukemia virus (MuLV)-infected C57BL/6 mice to model AIDS and thereby study the immunological changes in human retrovirus infection. Production of Th1 cytokines (IL-2 and IFN-γ) was suppressed, whereas Th2 cytokine production (IL-4, IL-5, IL-6, and IL-10) was enhanced in spleen and mesenteric lymph nodes (MLN) during retrovirus infection. However, increased secretion of IFN-γ in the MLN of retrovirus-infected mice may represent incremental production and release by non-Th1 cells. Lymphoid cell population changes in gut-associated lymphoid tissues (GALT) were documented 4 months after retrovirus infection. Total lymphoid cell numbers decreased in Peyer's patches and CD4⁺ cell numbers decreased in the intestinal lamina propria (ILP). Total lymphoid cell numbers increased in MLN but the relative percentages of surface IgA⁺, cytoplasmic IgA⁺ (cIgA⁺), and cIgM⁺ cells were decreased. Cryptosporidium infestation in retrovirus-infected mice decreased following the administration of pooled bovine colostrum containing a high titer of antibody demonstrating the potential efficacy of passive humoral immunity. Changes in the host cellular immune apparatus, following Cryptosporidium infection, were as follows: (1) increased γδ-TCR⁺ cells in the ILP 6 and 10 days post-infection, (2) decreased CD4⁺ cells in the ILP and intraepithelium 10 days post-infection, (3) reduced IgA⁺ and IgG⁺ cells in

A murine model of acquired immunodeficiency syndrome (AIDS) was developed by infecting C57BL/6 mice with murine leukemia retrovirus LP-BM5. Murine AIDS shares many features with human AIDS. Murine and human AIDS cause impairment of cell-mediated and humoral immune responses, and increase risk of opportunistic infection such as Streptococcus pneumoniae. Cofactors such as ethanol may determine the severity of the retrovirus infection and the rate of progression to AIDS. Changes in nutritional status due to retrovirus infection or ethanol consumption, can play an important role in immunomodulation in the animal. Immunomodulation observed in animals with chronic ethanol ingestion is associated with age of the animal, the nutritional composition of the diet, and the amount of ethanol consumed. Young mice are more sensitive to the immunomodulating effects of ethanol and diet than mature mice. The percentage of B cells in mature mice was significantly increased with consumption of nutritionally superoptimal diet containing ethanol while ethanol ingestion with a nutritionally inadequate diet severely decreased the percentage of B cells when compared to control or pair-feeding. Cytokine secretion, and natural killer cell and phagocytic activities were modulated by ethanol as well as by the nutritional quality of the diet. Both retrovirus infection and ethanol consumption affected survival rate after Streptococcus pneumoniae infection in mice. Chronic ethanol consumption, but not retrovirus infection resulted in significant reduction in serum level of anti pneumococcal polysaccharide antibody which in combination with complement system make up an important part of host defense against S. pneumoniae. However, retrovirus infection significantly reduced resistance to S. pneumoniae. Retrovirus infected mice fed a diet containing a high concentration of ethanol for short term exhibited a greater resistance to S. pneumoniae infection than mice fed diets with low concentration or no

The mechanism by which vitamin A (VA, retinol) potentiates the hepatotoxicity of carbon tetrachloride (CCl₄) in male Srague-Dawley rats was investigated. The toxicity of single and repeated doses of CCl₄ was potentiated in rats following VA treatment. CCl₄-induced hepatotoxicity was completely eliminated in control and VA-treated rats by 1-aminobenzotriazole, a cytochrome P-450 inhibitor, indicating that CCl₄ metabolism was necessary to achieve potentiation. To determine if VA-potentiated CCl₄ hepatotoxicity involves retinol activation of Kupffer cells (KC), various parameters were measured as indicators of KC function. In vitro assays using populations of KC demonstrated that phagocytosis and free radical release were increased in KC isolated from VA-treated rats. A novel electrooptical technique for measuring release of superoxide anion (•O₂-) from individual KC was developed. It was demonstrated that KC are a heterogeneous population, each responding separately to a common stimulus. To examine if the mechanism by which VA potentiates CCl₄ hepatotoxicity is common to model systems in addition to Sprague-Dawley rats, four separate mice strains were also tested. VA pretreatment dramatically protected against CCl₄ toxicity in each mouse strain tested. These data support the hypothesis that in rats, release of reactive oxygen intermediates from KC is intimately involved in the mechanism by which VA potentiates CCl₄ hepatotoxicity.