Autoimmune diseases induction

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

Penicillamine onset may be seen in 1 to 3 months, and most responses occur within 6 months. Early adverse effects include skin rash, metallic taste, hypogeusia, stomatitis, anorexia, nausea, vomiting, and dyspepsia. Glomerulonephritis may occur, which manifests as proteinuria and hematuria. Penicillamine is usually reserved for patients who are resistant to other therapies because of the rare but potentially serious induction of autoimmune diseases (e.g., Goodpasture s syndrome, myasthenia gravis). 

Induction of Autoimmune Disease Genes Versus Environment.426... 

INDUCTION OF AUTOIMMUNE DISEASE GENES VERSUS ENVIRONMENT... 

The mechanism most commonly invoked to explain the association of infection with autoimmune disease is molecular mimicry that is, the concept that antigens (or more properly, epitopes) of the microorganism closely resemble self-antigens.50 The induction of an immune response to the microbial antigen thus results in cross-reactivity with selfantigens and the induction of autoimmunity. Although epitope specific cross-reactivity has been shown in some animal models,48,51 53 molecular mimicry is clearly demonstrated to be the causative mechanism in few, if any, human diseases.3 54,55... 

Many environmental factors have been implicated in the induction of autoimmunity. One dietary component, iodine, has been well studied as a factor that increases autoimmune thyroid disease.67 68 Based on studies in the OS chicken, the increasing prevalence of autoimmune thyroid disease observed in U.S. and Western European populations has been ascribed to increased use of iodized salt.69 Experimentally, it can be shown that iodinated thyroglobulin is a more potent autoantigen than the equivalent noniodinated molecule. Food additives or pesticides may also be important in contributing to the development of autoimmune disease in susceptible individuals.70... 

One of the primary reasons ultraviolet radiation is of interest in the context of autoimmune diseases is because of induction of photosensitive cutaneous lesions (cutaneous lupus erythematosus)82 and dermatomyositis.83 A recent global evaluation of the frequency of dermatomyositis and associated autoantibodies in referral centers around the world showed a positive correlation with the intensity of ultraviolet irradiation at those locations.84... 

Regarding the cellular phenomenon giving the autoimmune disease in Balb mice, the importance of T cells in the induction of the immune-complex disease was found while in another strain, SJL mice, a polyclonal B cell activation was obtained however, the importance of T cells could not be excluded [209],... 

Kamradt T, Goggel R, Erb KJ Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection. Trends Immunol 2005 26 260-267. 

Based on the kno vledge of the processes of T cell sensitization by chemicals and the importance of T cells in induction of autoimmune diseases a number of key indicators of autoimmunogenic compounds can be defined. These include the possibility to be subject of metabolic conversion (either intra- or extra-hepatically), the capacity to activate dendritic cells, to induce cytokine production (in any cell type), or the potency to cause cell stress or cell death. Most of these processes can be studied in vitro, but none of the available methods have been tested for this purpose and often chemicals may behave completely different in vitro than in vivo. However, much can be learned from initiatives to design alternative methods for contact allergens, as many of these basic processes that lead to T cell sensitization are similar for allergenic and autoimmunogenic chemicals. 

With regard to safety, pDNA has been found to be safe and well-tolerated in a variety of species. In mice, the repeated i.m. administration of pDNA has not been found to be associated with the induction of autoimmune disease in animals prone to developing autoimmune disease (Mor et al., 1997). In mice and rabbits, the repeated i.m. or combined i.m./intradermal (i.d.) administration of pDNA-based malaria... 

Mucosal adjuvant and vaccine delivery system development is an area of importance for improving public health. Mucosal immunization can serve in the future in increasing mucosal immune function, induction of protective immunity against infections, and induction of tolerance or modifying autoimmune disorders, allergies, and autoimmune diseases. Development of oral vaccines would have large implications for rural and remote populations where access to trained medical staff to administer vaccines by injection can be lacking. 

Miossec P. Cytokines and autoimmune diseases from the control of autoimmune diseases with anti-cytokine treatment to the induction of autoimmunity with cytokine treatment. In House RV, Descotes J, eds. Cytokines in Human Health Immu-notoxicology, Pathology and Human Health. Totowa NJ Humana Press, 2007 233-58. 

In theory, all genes coding for products that are involved in the induction and maintenance of self-tolerance and in regulating immune effector functions as well as organ-specific functions may be involved in defining individual susceptibility. The most clearly established genetic association is with specific alleles within the MHC gene complex. However, with rare exceptions, a specific MHC haplotype is not sufficient for development of autoimmune disease. 

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