| LICENSEE | This data is not available for free |
| LICENSOR | This data is not available for free |
| LITERATURE REF. | This data is not available for free |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | February 1, 2000 |
| PATENT TITLE |
Methods of treating animals to maintain or increase CD-4 and CD-8 cell populations |
| PATENT ABSTRACT | Methods of treating animals to maintain or elevate CD-4 and CD-8 cell levels and to prevent or alleviate the adverse effects on the animal caused by the production or exogenous administration of tumor necrosis factor (TNF) or by a virus consist of administering to the animal a safe and effective amount of a conjugated linoleic acid (CLA) or a substance which is converted in the animal into CLA. A method of preparing CLA employing a bacteria isolated from a rat colon also is disclosed |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | October 13, 1998 |
| PATENT REFERENCES CITED |
Begin, M.E., et al., "Plasma Fatty Acid Levels in Patients with Acquired Immune Deficiency Syndrome and in Controls," Prostaglandins Leukotrienes and Essential Fatty Acids, 37:135-137 (1989). Chin, Sou F., et al., "Conjugated Linoleic Acid (9,11- and 10,12- Octadecadienoic Acid) Is Produced in Conventional but Not Germ-Free Rats Fed Linoleic Acid," Nutrient metabolism, pp. 694-701 (1994). Chin et al., "Synthesis of CLA by Intestinal Microorganisms," FASEB J. 7, A169 (1993). Chin et al., "Synthesis of CLA by Intestinal Microorganisms," Food Research Institute, 1992 Annual Report, p. 139-140. Cook, Mark E., "Exogenous Antigen Challenge and Its Effect on Nutrient Metabolism," Proceedings American Association of Swine Practitioners 25th Annual Meeting (1994). Cook, et al., "Immune Modulation by Altered Nutrient Metabolism: Nutritional Control of Immune-Induced Growth Depression: Symposium: The Microenvironment of Immune Tissue," Poultry Science, 72:1301-1305 (1993). Das, U.N., "Can Essential Fatty Acid Deficiency Predispose to AIDS?", Can. Med. Assoc. J., 132:900-902 (Apr. 15, 1995). Eyssen et al., "Biotransformation of Linoleic Acid and Bile Acids by Eubacterium lentum," Applied and Environmental Microbiology, 47:39-43 (1984). Fairbank et al., "Octadeca-9-11 Dienoic Acid in Diagnosis of Cervical Intraepithelial Neoplasia," Lancet p. 329 (1988). Fujimoto et al., "Biohydrogenation of Linoleic Acid by Anaerobic Bacteria Isolated from Rumen," Biosci. Biotech. Biochem. 57:1026-1027 (1993). Ha, Y.L., et al., "Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid," Carcinogenesis, 8(12):1881-1887 (1987). Ha, Y.L., et al., "Newly Recognized Anticarcinogenic Fatty Acids: Identification and Quantification in Natural and Processed Cheese," J. Agric. Food Chem., 37(1):75-81 (1989). Haumann, B., "Conjugated Linoleic acid offers research promise," Inform. 7:152-159 (1996). Ip et al., "Mammary Cancer Prevention by Conjugated Dienoic Derivative of Linoleic Acid," Cancer Research, 51,6118-6124 (1991). Jack et al., "Serum octadeca-9, 11 dienoic-acid--an assay of free radical activity or a result of bacterial production?," Clinica Chimica Acta, 224:139-146 (1994). Kemp et al., "The Hydrogenation of Unsaturated Fatty Acids by Five Bacterial Isolates from the Sheep Rumen, Including a New Species," Journal of General Microbiology, 90:100-114 (1975). Kepler et al., "Biohydrogenation of Unsaturated Fatty Acids," Journal of Biological Chemistry, 245:3612-3620 (1970). Klein, A., et al., "Progress of HIV Infection And Changes in The Lipid Membrane Structure of CD4+Cells," AIDS, 6(3):332-333 (1992). Kohn, A., et al., "Unsaturated Free Fatty Acids Inactivate Animal Enveloped Viruses," Archives of Virology, 66:301-307 (1980). Kumar, G. Sravan, et al., "Effect of n-6 and n-3 Fatty Acids on the Proliferation of Human Lymphocytes and Their Secretion of TNF-a and IL-2 in Vitro," Nutrition Research, 12:815-823 (1992). Lee et al., "Conjugated Linoleic acid and atherosclerosis in rabbits," Atherosclerosis, 108:19-25 (1994). The Merck Index, Tenth Edition (1983), p. 790. Michel, et al., "Interaction of Conjugated Dienoic Derivatives of Linoleic Acid with .beta.-Carotene on Cellular Host Defense," Fed. Am. Soc. Exp. Biol. J., 6:A1102 (1992). Miller, et al., "Feeding Conjugated Linoleic Acid to Animals Partially Overcomes Catabolic Response Due to Endotoxin Injection," Biochemical and Biophysical Research Communications, 198(3):1107-1112 (1994). Mills et al., "Hygrogenation of C.sub.18 Unsaturated Fatty Acids by Pure Cultures of A Rumen Micrococcus," Aust. J. Biol. Sci., 23:1109-1113 (1970). Nicolosi et al., "Dietary Conjugated Linoleic Acid Reduces Aortic Fatty Streak Formation Greater Than Linoleic Acid in Hypercholesterolemic Hamsters," Circulation, 88(suppl):24-58 (1993). Pariza, M.W., Food Research Institute 1988 Annual Fall Meeting, (Oct. 12, 1988). Peck, Michael D., et al., "The Esterified Plasma Fatty Acid Profile Is Altered in Early HIV-1 infection," Lipids, 28(7):593-597(1993). Thompson et al., "Measurement of The Diene Conjugated Form of Linoleic Acid in Plasma by High Performance Liquid Chromatography: A Questionable Non-Invasive Assay of Free Radical Activity?," Chem. Biol. Interactions, 55:357-366 (1985). Uchida, K., "Occurrence of Conjugated Dienoic Fatty Acids in The Cellular Lipids of Pediococcus homari," Agr. Biol. Chem., 39(2):561-563 (1975). Verhulst et al., "Isomerization of Polyunsaturated long Chain Fatty Acids of Propionibacteria," System. Appl. Microbiol., 9:12-15 (1987). Verhulst et al., "Biohydrogenation of Linoleic Acid by Clostridium sporogenes, Clostridium bifermentans, Clostridium sordellii and Baceriodes sp.," FEMS Microbiology Ecology, 31:255-259 (1985). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
We claim: 1. A method of preparing a conjugated linoleic acid (CLA) which comprises incubating a Lactobacillus strain that converts linoleic acid to a CLA, in a nutrient medium that comprises free linoleic acid for a time sufficient to convert linoleic acid to CLA. 2. A conjugated linoleic acid enriched milk product made by the process of claim 1 in which the medium is milk based. 3. The method of claim 1 wherein the Lactobacillus is incubated under aerobic conditions. 4. The method of claim 1, wherein the Lactobacillus is incubated under anaerobic conditions. 5. The method of claim 1, wherein the Lactobacillus is ATCC 55739. |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The present application generally relates to methods of treating animals, including humans. More particularly, it relates to methods of treating animals by maintaining or increasing the CD-4 and CD-8 lymphocyte cell populations or levels in said animals. It is known that maintaining or increasing CD-4 and CD-8 cell populations in an animal can benefit its immune system. BACKGROUND OF THE INVENTION Researchers have observed anorexia and weight loss or reduction in weight gain in humans and animals that have been exposed to immune stimulants, such as endotoxin (LPS). The intraperitoneal injection of lipopolysaccharide (i.e. endotoxin) into chickens decreases food intake and growth rate for 24 hours, alters nutrient metabolism, and induces fever. Recent studies (Klasing et al., 1987, J Nutr. 117:1629) have confirmed that the vaccination of domestic fowl with several immune stimulants also can result in a substantial reduction in feed intake and induce weight loss or decrease in weight gain. In a study recently conducted with white Pekin ducks, two vaccinations reduced final carcass weight by as much as 0.4 lbs./bird and breast meat by 0.075 lbs./bird. Broilers and Single Comb White Leghorns (egg laying chickens) also have been observed to have reduced weight gains following immune stimulation. The potential losses due to immune stimulation costs the poultry industry millions of dollars per year. At the present time, antibiotics are used to prevent such weight loss, but the use of antibiotics for this purpose is expensive and not without disadvantages. In a similar manner anorexia, weight loss, and reduced growth of humans that are subjected to chronic immune stimulation because of infections, surgery, or exposure to immune stimulants is devastating to health and well being. The mechanism by which immune stimulation causes anorexia, weight loss and reduced growth is known to be mediated by products, such as catabolic hormones, released following immune stimulation (e.g., the macrophage cytokine known as interleukin-1 or IL-1). The production of IL-1 from macrophages simultaneously stimulates T-cells to release IL-2, an anticarcinogenic compound which is desirable, but the release of IL-1 and other catabolic hormones from stimulated macrophages and possibly other immune-regulated cells induces an undesirable systemic reduction in skeletal muscle synthesis and increased muscle degradation resulting in weight loss or a decline in weight gain. Thus, while IL-1 and related immune hormones are essential cytokines for immune function, their systemic hormonal effects are devastating and have prevented its acceptance for immune therapy. It is known that other biological products produced by immune cells, such as tumor necrosis factor (TNF) also can cause adverse physiological changes in animals, including anorexia and cachexia, and it has been observed that viral infections of animals can have similar adverse effects on the animals. It also has been observed that viral infections, especially HIV infections, can undesirably deplete the CD-4 (helper T cells) and CD-8 (cytotoxic T cells) cell populations in infected animals, including humans. It would be advantageous to have methods of maintaining or elevating CD-4 and CD-8 cell populations in animals to bolster or benefit their immune systems and methods for preventing or alleviating the adverse effects of the production or exogenous administration of TNF and viral infections in animals. BRIEF SUMMARY OF THE INVENTION It is one object of the present invention to disclose a method of maintaining or elevating CD-4 and CD-8 cell levels in animals to bolster or benefit their immune systems. It also is an object of the present invention to disclose a method for preventing or alleviating the adverse effects caused by the production or exogenous administration of TNF in animals, including humans. It is another object to disclose a method of preventing or alleviating the adverse effects caused by viral infections in animals, including humans. It also is an object to disclose novel methods of producing conjugated linoleic acids (CLA) for use in such methods. We have discovered that a method comprising the administration to an animal of safe and effective amounts of the conjugated linoleic acids 9,11-octadecadienoic acid and 10,12-octadecadienoic acid (CLA) or a substance that is converted in the animal to CLA can maintain and elevate the CD-4 and CD-8 cell levels and bolster or benefit the immune systems of those animals. We also have discovered that methods comprising the administration of the CLA prevent or alleviate the weight loss and other adverse effects that can result from the production and exogenous administration of TNF in animals, including humans, or from the infection of the animals, including humans, by viruses. It is possible that the beneficial effects of CLA in preventing or alleviating the adverse effects of TNF and virus are due to its ability to maintain or elevate CD-4 and CD-8 cell levels. We also have discovered a method of producing CLA which comprises using a strain of Lactobacillus which converts free linoleic acid into CLA. It will be apparent to those skilled in the art that the forementioned objects and other advantages may be achieved by the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS In the drawings: FIG. 1 is a graph showing the percent increase in the number of CD-4 positive cells in chicks given CLA as compared to control chicks (NT); FIG. 2 is a graph showing the percent increase in CD-4 positive cells (solid) and CD-8 positive cells (striped) in chicks given CLA and control chicks (NT); FIG. 3 is a graph like FIG. 2 showing the results of a second experiment; and FIG. 4 is a graph showing the differences in the TNF induced effects on body weight in control mice and on mice fed CLA. DESCRIPTION OF THE PREFERRED EMBODIMENT In the preferred method of the present invention for maintaining or increasing CD-4 and CD-8 cells, a safe and effective amount of conjugated linoleic acid (CLA) or a substance that is converted to CLA in the animal is administered to an animal, including a human, to maintain or elevate the CD-4 and/or CD-8 cell levels in the animal. In the preferred method of the present invention for preventing or alleviating the effects of TNF, a safe and effective amount of conjugated linoleic acid (CLA) or a substance that is converted to CLA in the animal is administered to an animal, including a human, which is likely to or is producing catabolic inducing levels of tumor necrosis factor (TNF) or which is likely to or is receiving catabolic inducing levels of exogenously administered TNF, to prevent weight loss and other adverse effects which can result from the systemic effects of TNF. Because of the differences in size and susceptibility of animals, including humans, to the adverse effects of systemically released or exogenously applied TNF, the amounts which are safe and effective will vary considerably. In the preferred method of the present invention for preventing or alleviating the adverse effects of viruses, a safe amount of CLA or a substance which is converted in the animal to CLA is administered to an animal, including a human, which is likely to be infected by a virus or vaccinated with a virus, or which has a viral infection. The amount which is administered, in addition, to being safe also is an amount which is effective to prevent or counteract the adverse effects of anorexia and other catabolic effects caused by the viral infection or vaccination. Since CLA is a natural food ingredient and it is relatively non-toxic, the amounts which can be administered in the methods of the invention are not critical as long as they are enough to be effective. In the preferred method for making CLA a biologically pure culture of Lactobacillus (ATCC No. 55739) is incubated in a medium containing essential nutrients and free linoleic acid under ambient conditions to produce CLA. |
| PATENT EXAMPLES | This data is not available for free |
| PATENT PHOTOCOPY | Available on request |
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