Immunosuppression animal disease models

Perform studies in animal transplant model of human disease (consider cell biology, anatomy, pathophysiology, biomechanics, etc immunosuppression regimen, identify limitations). 

Infectious Diseases. Resistance to a variety of organisms, including BCG, cryptococcus, and Candida, has been shown to be increased in immunosuppressed animals following in vivo treatment with TF5 (Collins and Auclair, 1979 Collins and Morrison, 1979 Bistoni et al., 1982 Ishitsuka et al, 1983). The basis for this increased resistance may be explained by studies showing that mouse strains with low resistance to Candida or BCG have increased resistance and elevated production of two lymphokines, MIF and 7 interferon following in vivo treatment with TF5 (Neta and Salvin, 1983 Salvin and Neta, 1983). Similar results were seen with Taj. In another model, interferon production in response to Newcastle s disease virus infection was also increased by in vivo treatment with TF5 or Ta (Huang et al., 1982). 

One likely reason for the prevalence of helminths is their undoubted ability to down-regulate the host immune system at both the antigen-specific and polyclonal levels [3], In many chronic diseases, such as schistosomiasis and lymphatic filariasis, peripheral blood T cells show dramatically impaired parasite antigen-specific responsiveness [4], as discussed in more detail below. Moreover, from early reports of immunosuppression in animal models of infection, to studies in Africa linking vaccine failure to heavy helminth infection, there is clear evidence that infections can diminish reactivity to bystander antigens, particularly with increasing intensity of... 

As is true for all biopharmaceuticals, toxicity studies should be performed in relevant animal models. For cellular therapies these models are often in animal models intended to mimic the human disease. When possible the intended human cells are utilized for assessments with or without low-dose immunosuppressants (e.g., lOmg/kg, i.p. dose of cyclosporine A in rats). The immunosuppressive drug is generally administered prior to the cell dose and extended for a specified period after the transplant. In cases where it is not feasible to use the intended clinical material, largely due to the inability of the cells to engraft sufficiently into the host, analogous cells can be used to assess preclinical safety and activity. In such cases it is important to understand the potential impact of any differences between the analogous product and the clinical product in order to improve extrapolation of safe and active cell doses to humans. 

Relatively non-specific T cell immunosuppression has been successful in animal models. Treatment of hypersensitivity pneumonitis in mice with cyclosporin A led to improvement of the disease as seen by an abrogation of the increase in lung index, lack of IL-1 and TNFa release in BAL (Denis etal., 1992). However, this drug has not proven to be useful in clinical lung fibrosis in humans. 

Fungi produce a number of inhibitors of CerS. The most studied are the fumonisins, which are produced by Fusarium verticillioides, a common contaminant of com. Fumonisins were first discovered in a search for the causal factor(s) for human esophageal cancer in the Transkei region of South Africa and two diseases encountered in agricultural animals that eat contaminated food (W.F.O. Marasas, 2001). They were subsequently found to have many pathological effects liver and kidney toxicity, renal cancer, immunosuppression (and in some cases immunostimulation), and birth defects, with the latter being seen not only in studies with experimental models (W.F.O. Marasas,... 

Flavones and flavonols can exert the anti-inflammatory activity in many animal models and are useful in allograft rejection and rheumatic diseases as an immunosuppressive agent A number of reports have been published which demonstrate that flavones and flavonols, such as quercetin, myricetin, and fisetin, can modulate arachidonic acid metabolism via the inhibition of cyclooxygenase and lipoxygenase activity [130, 131], Quercetin prevents inunune cells and inhibits both the production and release of histamine and is useful in allergic conditions like asthma, hay fever, etc. [132],... 

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