Immune complex diseases animal model

With respect to studies in animal models which dissect the mechanisms of formation, localization, and fate of immune complexes, the mechanisms by which they elicit an inflammatory response, and their biologic activities, we provide little more than summary information required to understand the concept of immune complex disease and the principles of the tests. For more detailed information, the reader is referred to several excellent reviews (C14, H2, Til, Ul, W12). 

Animal models of disease, whether naturally occurring or artificially induced, provide valuable insights into human disease and allow rigidly controlled studies that are not possible in humans. Probably the most intensively studied model of an immune complex disease is the spontaneous lupuslike disease that occurs in certain inbred strains of mice, especially the (NZB x NZW) F, hybrid. Its study has provided insights with respect to genetic predisposition (H25), the role of endogenous retroviruses (D8), the influence of sex hormones (R9), the identification of T suppressor cell abnormalities (T3), and the propensity to form certain autoantibodies, especially to double-stranded DNA (S36) and to the RNA-protein complex, Sm (E2). Though animal studies are not the subject of this review, we emphasize that the entire concept and framework by which we view immune complex disease in humans are based on initial observations in animals. 

The penultimate step in drug development is the testing of the drug candidate in animal models of disease, where all the complex interactions that underlie pathophysiological mechanisms take place. It is important that animal models not only manifest the relevant disease phenotype observed in humans, but that the underlying innate and adaptive immune responses are similar to the human disease. In the case of leishmaniasis, there are reasonably good animal models for some, but not all of the cutaneous forms. The animal models for visceral leishmaniasis are less satisfaaory. Nonetheless, the animal models for leishmaniasis are considerably better than those for other parasitic diseases. 

Studies in our laboratory show that a basal diet composed of lipid exclusively from fish oil, instead of safflower oil, fed to autoimmune mice suppresses the progression of renal injury and prolongs survival. In MRL-/pr mice, the most aggressive model of lupus, a 20% fish oil diet suppresses the increase in proteinuria, the localization of immune complexes in the glomerulus and the development of renal pathology ". In the NZB x NZW mice with a less virulent form of this illness, a diet rich in fish oil can prevent renal injury when animals are started on it prior to the expression of renal disease and can arrest the progression and reduce mortality when treatment is delayed until the mice are mildly proteinuric ". These data suggest that a fish diet is not only prophylactically beneficial but also offers therapeutic promise. 

Malnutrition is a complex disease, rarely characterized ty a well defined deficit of specific nutrients. For example, the protein composition of the diet often influences the trace element content. Differences between animal models, in which protein deficiency often stimulates cell-mediated immunity, and human studies, which have often indicated depressed cel 1-mediated immunity in protein restriction, can be rationalized by deficiencies of zinc which occur in protein-poor human diets. Consistent with this picture, most amino acid deficiencies exert less influence on the immune response than on overall growth rate (Hill, 1982). 

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