Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin
Patent
1995-03-30
1998-10-27
Ulm, John
Drug, bio-affecting and body treating compositions
Lymphokine
Interleukin
530351, 514866, A61K 3820, C07K 1454
Patent
active
058275134
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the use of interleukin-10 (IL-10), formerly known as cytokine synthesis inhibitory factor (CSIF), for the treatment or prevention of insulin-dependent (type 1) diabetes mellitus.
BACKGROUND OF THE INVENTION
Immune responses to an antigen are classified as being predominantly either cell-mediated, exemplified by the phenomenon of delayed-type hypersensitivity (DTH), or humoral, exemplified by the production of antibodies. Cell-mediated immunity is of paramount importance for the rejection of tumors and for recovery from many viral, bacterial, protozoan and fungal infections. In contrast, a humoral immune response is the most effective form of immunity for eliminating toxins and invading organisms from circulation.
It has been observed that for different antigens one or the other of these two responses often predominates in a mutually exclusive fashion, and that the severity of some diseases, e.g., leprosy, leishmaniasis, and some types of autoimmunity, may be due the inappropriate dominance of one class (1987); Mosmann et al., Ann. Rev. Immunol. 7:145-173 (1989); Parish, Transplant. Rev. 13:35-66 (1972); Liew, Immunol. Today 10:40-45 (1989)!.
It has further been observed that sets of cytokines are separately J. Immunol. 138:3688-3694 (1987); Mosmann et al. 1987 and 1989, supra!, and it is thought that diseases associated with these classes of response are caused by the inappropriate production of the associated sets of cytokines.
For example, a large body of evidence suggests that excessive production of gamma interferon (IFN-.gamma.) is responsible for major histocompatibility Med. 301:5-8 (1979) (elevated serum levels of IFN-.gamma. correlated with autoimmunity); Basham et al., J. Immunol. 130:14921494 (1983) (IFN-.gamma. can increase MHC gene product expression); Battazzo et al., Lancet, pgs. 1115-1119 (Nov. 12, 1983) (aberrant MHC gene product expression correlated with some forms of autoimmunity); Hooks et al., Ann, N.Y. Acad. Sci., Vol. , pgs. 21-32 (1980) (higher IFN-.gamma. levels correlated to greater severity of disease in SLE patients, and histamine-release enhancing activity of interferon can be inhibited by antiinterferon sera); Iwatani et al., J. Clin. Endocrin. Metabol. 63:695-708 (1986) (anti-IFN-.gamma. monoclonal antibody eliminated the ability of leucoagglutinin-stimulated T cells to induce HLA-DR expression)!. It is hypothesized that excess IFN-.gamma. causes the inappropriate expression of MHC gene products which, in turn, causes autoimmune reactions against the tissues whose cells are inappropriately expressing the MHC products and displaying autoantigens in the context of the products.
Insulin-dependent diabetes mellitus (IDDM), also known as juvenile or type 1 diabetes, is an autoimmune disorder characterized by cellular infiltration (insulitis) of the pancreatic islets of Langerhans (pancreatic .beta. cells). It is believed that IDDM is the result of cell-mediated autoimmune processes and is restricted to particular Class II HLA types.
The non-obese diabetic (NOD) mouse is also known to develop IDDM. Spontaneous IDDM occurs with an incidence of 70-90% in female NOD mice at 18-25 weeks of age. Because this disease exhibits all of the pathological and autoimmune manifestations of the human disease, NOD mice serve as an excellent model for the identification of agents that might prevent IDDM or ameliorate the effects of the disease.
In humans, development of IDDM can be conceptually divided into stages, beginning with a human leukocyte antigen (HLA)-restricted genetic susceptibility. In some genetically susceptible individuals, a triggering event activates both cellular and humoral autoimmunity.
Glucose-stimulated insulin secretion and .beta. cell mass diminish as anti-islet autoimmunity progresses. This process culminates in overt diabetes when only residual .beta. cell mass (estimated at <10%) remains. Complete .beta. cell destruction typically follows within months to years of diagnosis.
Most current efforts to treat IDDM involve the use of broad immu
REFERENCES:
Cohen, J. Science 270:908, 1995.
Pankewycz et al. Eur. J. Immunol 22: 2017-2023, 1992.
Sarvetnick et al. Ped. Res. 33: 51, 1993.
Wogensen et al. J. Exp. Med 179: 1379-1384, 1994.
Lee et al. J. Clin. Invest. 93: 1332-1338, 1994.
Moritani et al. Intern. Immunol. 6: 1927-1936, 1994.
Moratini et al., 1996, J. Clin. Invest. 98(8):1851-1859.
Pennline et al., 1994, Clinical Immunology and Immunopathology 71(2):169-175.
Bond Martha W.
Moore Kevin W.
Pennline Kenneth
Vieira Paulo J. M.
Dulak Norman C.
Foulke Cynthia L.
Saoud Christine
Schering Corporation
Ulm John
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