Selective regulation of B lymphocyte precursors by hormones

• US 5,494,899 A
• Filed: 04/07/1994
• Issued: 02/27/1996
• Est. Priority Date: 04/07/1993
• Status: Expired due to Term

• Current Assignee: Oklahoma Medical Research Foundation
• Original Assignee: Oklahoma Medical Research Foundation
• Inventors: Medina, Kay, Kincade, Paul W.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): DEGEN, NANCY JILL
• Application Number:
  US08/224,236
• Time in Patent Office: 691 Days
• Field of Search: 514/21, 514/841, 514/843, 514/177, 514/182, 530/399, 530/850, 530/851, 530/852, 530/853, 530/854
• US Class Current: 514/10.2
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C12N 2501/392 Sexual steroids
• CPC Class Codes: C12N 5/0635 B lymphocytes
• CPC Class Codes: G01N 33/743 Steroid hormones
• CPC Class Codes: Y10S 530/85 Reproductive organs or embryos
• CPC Class Codes: Y10S 530/851 Placenta; amniotic fluid
• CPC Class Codes: Y10S 530/852 Sperm
• CPC Class Codes: Y10S 530/853 Ovary; eggs; embryos
• CPC Class Codes: Y10S 530/854 Glands

Abstract

It has been determined that estrogen and other hormones elevated in pregnancy induce a specific modulation of lymphocyte precursor cell production. The immune system of an animal or bone marrow cells in culture can therefore be modulated in a specific manner by administration of hormones elevated during pregnancy, such as estrogen and estrogen-like compounds or compounds that interfere with the synthesis or activity of these hormones, to increase or decrease production of B lymphocyte precursor cells.

Claims

1. A method for modulating production of committed mammalian B lymphocyte precursor cells in an animal that has normal bone marrow comprising exposing the cells to a hormone selected from the group consisting of hormones elevated during pregnancy, synthetic analogues of the hormones elevated during pregnancy, eliciting agents of the hormones elevated during pregnancy, and agents that interfere with the synthesis or activity of the hormones elevated during pregnancy, in an amount effective to alter selectively production of B lymphocyte precursor cells by proliferation or differentiation as compared with proliferation of mature B lymphocytes.

2. The method of claim 1, wherein the hormone is selected from the group of natural and synthetic hormones consisting of estrogen, estrone, estradiol, estriol, progesterone, and combinations thereof, and the amount is effective to inhibit production of B lymphocyte precursor cells by proliferation or differentiation.

3. The method of claim 1, wherein the agent that interferes with the synthesis or activity of the hormones elevated during pregnancy is selected from the group consisting of agonists, antagonists, competitive inhibitors, inactivators, and blockers, alone or in combination, of the hormones elevated during pregnancy.

4. The method of claim 1, wherein the hormone is administered to cells in culture.

5. The method of claims 4, wherein the cells are bone marrow cells in culture.

6. The method of claim 1, wherein the hormone is an agent that interferes with the synthesis and activity of the hormones elevated during pregnancy and the amount is effective to increase production of B lymphocyte precursor cells by proliferation or differentiation.

7. The method of claim 6, wherein the agent is selected from the group consisting of RU 486, ICI 182,780, aromatase inhibitors, and gonadotropin releasing hormone agonists.

8. The method of claim 7, wherein the aromatase inhibitors are selected from the group consisting of 1,4,6-androstatriene-3,17-dione and 4-hydroxyandrostenedione.

9. The method of claim 1, wherein the hormone is selected from the group consisting of chorionic gonadotropin, hormone eliciting agents, agents that interfere with the synthesis or activity of the hormones elevated during pregnancy, and combinations thereof and the amount is effective to manipulate production of B lymphocyte precursor cells by proliferation or differentiation in animals and man.

10. The method of claim 9, wherein the hormone is administered to a patient in need of treatment to modulate production of committed mammalian B lymphocyte precursor cells.

11. The method of claims 10, wherein the patient has an autoimmune disorder and the amount is effective to decrease production of B lymphocyte precursor cells by proliferation or differentiation and thereby decrease production of mature B lymphocytes that secrete autoantibodies.

12. The method of claim 10, wherein the patient has a humoral immune deficiency disease and the amount is effective to increase production of B lymphocyte precursor cells by proliferation or differentiation and thereby increase production of mature B lymphocytes in an amount effective to alleviate the symptoms of the immune deficiency disease.

13. The method of claims 10, further comprising administering to a patient in need of treatment to modulate production of committed mammalian B lymphocyte precursor cells a hormone selected from the group consisting of chorionic gonadotropin, hormone eliciting agents, agents that interfere with the synthesis or activity of the hormones elevated during pregnancy, and combinations thereof in an amount effective to increase calcium deposition by stromal cells of bone marrow.