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An autoimmune disease can be characterized by the presence of anti-self antibodies (xe2x80x9cautoantibodiesxe2x80x9d) or self-reactive B- and T-cell clones which are generally not observed in animals that do not have such a disease. The autoantibodies form immune complexes that become trapped in tissues and organs and thereby attract macrophages which can physically damage the animal""s tissues or organs. For example, in the non-limiting case of a damaged kidney, protein molecules normally prevented from leaving the kidney in urine are instead excreted in the urine. A relatively common autoimmune disease is lupus, a chronic inflammatory disease that can affect various parts of the body, especially skin, joints, blood, and kidneys. More than 16,000 Americans develop lupus each year. It is estimated that 500,000 to 1.5 million Americans have been diagnosed with lupus.
Three types of lupus are known: systemic lupus (sometimes called systemic lupus erythematosus or xe2x80x9cSLExe2x80x9d), discoid lupus, and drug-induced lupus. SLE can affect almost any organ or system of the body. Discoid lupus is always limited to the skin. Approximately 10 percent of discoid lupus evolve into the systemic form of the disease. Drug-induced lupus occurs after the use of certain prescribed drugs. The symptoms of drug-induced lupus are similar to those of systemic lupus. The symptoms usually fade when the medications are discontinued.
SLE is caused by defects in immune regulation that result in hyperactive T and B lymphocytes, which in turn causes widespread tissue damage by cell-mediated immune responses, autoantibodies or immune complexes. A hallmark of SLE pathogenesis is the presence of serum autoantibodies against nuclear components as a result of immune dysregulation. For example, IgG autoantibodies to DNA are responsible for the formation of immune complexes in SLE glomerulonephritis. Steward M W et al., Clin. Exp. Immunol. 26, 363 (1976); Lambert P H et al., J. of Exp. Med. 127, 507 (1968). The immune complexes are deposited along the wall in the small blood vessel of kidney, resulting in glomerulonephritis. About a third of patients with lupus develop nephritis which requires medical evaluation and treatment. Glomerular leakage of plasma proteins makes proteinuria an indicator of kidney damage by autoantibody immune complexes.
Conjugated linoleic acid (xe2x80x9cCLAxe2x80x9d) is a group of positional and geometrical isomers of linoleic acid. Ha Y L et al., Carcinogenesis 8, 1881 (1987). These naturally occurring fatty acids are found in beef and dairy products due to ruminal isomerization of linoleic acid. Chin S F et al., Journal ofNutrition 124, 694 (1994). CLA has been shown to modulate immune response, Cook M E et al., Poult. Sci. 72, 1301 (1993); Chew B P et al., Anticancer Res. 17:1099 (1997); Miller C C et al., Res. Commun. 198, 1107 (1994), to reduce body fat, Park Y et al., Lipids 32, 853 (1997), and to have anti-carcinogenic and anti-atherosclerotic activity. Ha Y L et al., Carcinogenesis 8, 1881 (1987); Nicolosi R J et al., Artery 22, 266 (1997).
The active forms of UA include, in addition to the free acids, the active isomers of CLA; non-toxic salts thereof; active esters and other chemical derivatives thereof; and mixtures thereof.
Yang M et al., Immunopharmacol Immunotoxicol. 22(3), 433-49 (2000) studied the effects of CLA on SLE using a well-established animal model for SLE, namely NZB/W F1 mice. The model has been used for more than thirty years and was originally described by Lambert P H et al., J. of Exp. Med. 127, 507 (1968). NZB/W F1 mice are commercially available from Harlan-Sprague-Dawley (Madison, Wis.). Yang et al. reported that dietary CLA fed from weaning onward accelerates the onset of proteinuria but does not significantly affect anti-DNA antibody production in those same mice. In the same study, the CLA-fed mice lived longer from the onset of proteinuria and lost less body weight than control mice. Despite this, the total lifespan of CLA-fed animals did not differ from that of control animals, in view of the accelerated onset of the autoimmune disorders. The authors did not study effects of CLA on life span and body weight loss in animals other than those who were fed CLA for a lifetime, beginning at weaning and made no predictions about whether a similar effect might be observed in animals fed CLA at another stage of life or at another stage of the autoimmune disorder.
In a first aspect, the invention is summarized in that a method for extending the survival time of a human or non-human animal having an autoimmune complex disease includes the step of administering to the animal after diagnosis of the autoimmune complex disease an amount of CLA effective to extend the life span of the animal.
In a related aspect, the invention is further summarized in that a method for reducing or preventing a body wasting effect in a human or non-human animal having an autoimmune complex disease includes the step of administering to the animal after diagnosis of the autoimmune complex disease an amount of CLA effective to reduce or prevent wasting of the animal.
It is an object of the invention to lessen the symptoms of an autoimmune disease on a human or non-human animal.
It is a feature of the invention that CLA can lessen the symptoms of an autoimrnune disease when administered after the effects of the disease on tissues and organs are observed.
Other objects, features and advantages will become apparent upon consideration of the following detailed description.