Method for reducing adverse effects of a human 70kDa mediator which results from endotoxin stimulation of macrophages

• US 6,419,927 B1
• Filed: 11/28/1994
• Issued: 07/16/2002
• Est. Priority Date: 09/08/1981
• Status: Expired due to Fees

• Current Assignee: Anthony Cerami, Masanobu Kawakami
• Original Assignee: Anthony Cerami, Masanobu Kawakami
• Inventors: Kawakami, Masanobu, Cerami, Anthony
• Primary Examiner(s): Spector, Lorraine
• Application Number:
  US08/345,226
• Time in Patent Office: 2,787 Days
• Field of Search: 424/145.1, 424/158.1, 424/130.1, 530/388.23, 530/389.2, 435/512
• US Class Current: 424/158.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 14/523 Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/38 against protease inhibitors of peptide structure
• CPC Class Codes: C12N 1/00 Microorganisms, e.g. protozoa; Compositions thereof medicinal preparations containing material from protozoa, bacteria or viruses A61K35/66, from algae A61K36/02, from fungi A61K36/06; preparing medicinal bacterial antigen or antibody compositions, e.g. bacterial vaccines, A61K39/00; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
• CPC Class Codes: C12N 2501/21 Chemokines, e.g. MIP-1, MIP-2, RANTES, MCP, PF-4
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12P 1/00 Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
• CPC Class Codes: C12R 2001/91 Cell lines ; Processes using cell lines
• CPC Class Codes: G01N 2333/52 Assays involving cytokines
• CPC Class Codes: G01N 2400/40 Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Provided are therapeutic uses of antibodies capable of neutralizing the adverse effects in humans of the about 70 kDa mediator produced upon invasive stimulation of macrophages by, e.g., contact with endotoxin.

Claims

1. A method for treating an adverse effect in a human of the about 70 kDa mediator substance which results from endotoxin stimulation of macrophages and which has the biological activity of suppression of lipoprotein lipase activity, said method comprising administering an antibody specifically reactive with said about 70 kDa mediator in an amount effective to neutralize suppression of an anabolic enzyme selected from the group consisting of lipoprotein lipase, acetyl coA carboxylase and fatty acid synthetase, said suppression induced by said about 70 kDa mediator.

3. The method of claim 1 or 2 wherein said antibody is a monoclonal antibody.

4. The method of claim 1 or 2 wherein the adverse effect neutralized is suppression of the anabolic enzymes lipoprotein lipase, acetyl CoA carboxylase and fatty acid synthetase.

5. The method of claim 1 or 2 wherein the human is suffering from shock.

6. The method of claim 1 or 2 wherein the human is suffering from cacbexia.

7. The method of claim 1 or 2 wherein the human is suffering from anemia associated with a chronic disease state.

8. The method of claim 7 wherein the chronic disease state is rheumatoid arthritis.

2. A method for treating an adverse effect in humans of the about 70 kDa mediator substance which results from endotoxin stimulation of macrophages and which has the biological activity of suppression of lipoprotein lipase activity, said method comprising administering an amount of an antibody capable of reducing inhibition of growth and differentiation of erythroid-committed cells wherein said inhibition is induced by said about 70 kDa mediator substance.