Interleukins autoimmunity

J (2001) Green tea polyphenol extract attenuates inflammation in interleukin-2-deficient mice, a model of autoimmunity , J Nutr, 131 (7), 2034-9. 

In terms of molecular biology, the attachment of Antigen Presenting Cells (APC) to T-cells can at this moment not be prevented. So a cure for chronic progressive autoimmune inflammatory disease is not feasible yet. Sooner or later disease in remission relapses when APC attach to T-cells with induction of Co-stimulatory pathways. The current therapeutic principles are to stop or slow down disease progression. This is achieved by elimination or at least a reduction of the pool of existing autoantibodies and of cytokines in the upstream systemic and downstream local interleukin independent and dependent pathways. 

Eizirik, D. L., Tracey, D. E., Bendtzen, K., and Sandler, S. (1992b). Role of receptor binding and gene transcription for both the stimulatory and inhibitory effects of interleukin-1 in pancreatic /3 cells. Autoimmunity 12, 127-133. 

Hypothyroidism, a condition in which the circulating concentrations of thyroid hormones are too low, is the most prevalent thyroid disease. Primary hypothyroidism, the commonest form, is an autoimmune disease (Hashimoto s thyroiditis) often associated with goitre. Like other autoimmune diseases, it is more prevalent in women (4 per 1000) than in men (1 per 1000). Other causes include thyroidectomy, radioac tive ablation and, in some countries, iodine deficiency. Hypothyroidism can also be caused by several drugs, including lithium, interleukin-2 and interferon. Secondary hypothyroidism is a disease caused by decreased secretion of TSH by the pituitary. 

Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism Interferon-a, interleukin-2, interferon-B, lithium, amiodarone... 

Maker AZ et al Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2 A phase I/II study. Ann Surg Oncol 2005 12 1004. 

Cytokines and antagonists (2—4), intercellular proteins produced by immune cells, play an important role in the regulation of immune responses. Cytokines are present in a variety of tissues under normal conditions. Through insufficient or excessive production, these macromolecules can mediate chronic inflammatory diseases. An inability to respond to cytokines, eg, interleukin 1 (IL-1) or interleukin 2 (IL-2), may lead to an immunosuppressive state, whereas over-production can result in severe shock, autoimmune disease, or immunopathological conditions, such as leukemia and rheumatoid arthritis (RA). Specific communications between immune cells are constantly modulated by naturally occurring inhibitors. 

Schuppert F, Rambusch E, Kirchner H, Atzpodien J, Kohn LD, von zur Muhlen A. Patients treated with interferon-alpha, interferon-beta, and interleukin-2 have a different thyroid autoantibody pattern than patients suffering from endogenous autoimmune thyroid disease. Thyroid 1997 7(6) 837-42. 

Nitta, Y., Tashiro, F., Tokui, M., Shimada, A., Takei, I., Tabayahsi, K. and Miyazaki, J.-I. (1998) Systemic delivery of interleukin-10 by intramuscular injection of expression plasmid DNA prevents autoimmune diabetes in nonobese diabetic mice. Hum. Gene Then, 9,1701-1707. 

Faust A, Rothe, H., Schade, U., Lampeter, E. and Kolb, H. (1996) Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. Transplantation, 62, 648-652. 

Mueller, R., Krahl, T. and Sarvetnick, N. (1996) Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. J. Exp. Med., 184,1093-1099. 

Cytokines are a potential way to modify the immune system in several situations because of their ability to act as immunoregulatory chemicals. For example, cytokines such as interferon-alpha and interleukin-2 can be administered to treat certain forms of cancer (see Chapter 36). Likewise, certain interferons can help control viral infections, and interferon-beta may be helpful in autoimmune diseases such as multiple sclerosis (see Chapter 34). Researchers continue to investigate how immune function can be manipulated to treat various diseases, and additional immune system modulators will almost certainly be forthcoming. 

Interleukin-1, pancreatic P cells, and insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus is an autoimmune disease that causes the gradual destruction of insulin-producing pancreatic P cells. It has been postulated that the infiltration of macrophages into the pancreatic islets plays a key role in the destruction of P cells and that cytokines, especially interleukin-1, which is released locally from macrophages, may be the toxic molecule causing this destruction. 

Babu et al. (2003) reported that a significant reduction in concanavalin A spleen lymphocytes proliferation in pregnant rats fed a 40% flaxseed diet. Spleen lymphocytes proliferation was significantly lower in a 90-day-old offspring on the 40% flaxseed diet and exposed to phytohemagglutinin. In both cases, interleukin-2 formation was not affected by flaxseed intake. The levels of LA and AA in serum and tissues combined with relatively constant interleukin-2 concentrations lead to the conclusion that flaxseed could be used in treating autoimmune diseases (Babu et al., 2003). 

Rabinovitch, A., Suarez-Pinzon, W. L., Sorensen, O., Bleackley, R. C., Power, R. F. and Rajotte, R. V. (1995). Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. Analysis of cytokine mRNA expression in the graft.Transplantation 60, 368-374. 

Autoimmune diseases have been reported to be more frequent in human subjects treated with several recombinant cytokines [38], For instance, increased titers or the new occurrence of autoantibodies have been observed in hepatitis C patients treated with the recombinant interferons-alpha (IFNa). Quite a few clinical case reports describe the development of organ-specific as well as systemic autoimmune diseases including systemic lupus erythematosus, insulin-dependent type I diabetes mellitus, autoimmune thrombocytopenia, autoimmune hemolytic anemia, myasthenia gravis, and autoimmune thyroiditis in patients under IFNa therapy. Although the mechanism involved is not fully elucidated, the available data support the pathogenic potential of IFNa in autoimmunity [31]. In contrast, autoimmune effects associated with IFNp therapy are thought to be of lesser concern based on the current clinical evidence [38], Thyroid autoimmunity in contrast to other autoimmune diseases is frequent in patients treated with recombinant interleukin-2 (rIL-2). Thus, among 281 previously euthyroid cancer patients treated with rIL-2, up to 41%... 

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