Use of Il-17 in the Treatment of Fertility-Related Disorders
The present invention is directed to methods for ameliorating reproductive disorders. More specifically, the present invention describes methods and compositions for using IL-17 in the treatment of various infertility-related defects.
1 . A method for treating a fertility-related disorder in a mammal comprising administering to said mammal a composition comprising IL-17 in an amount effective to alleviate the symptoms of said fertility related disorder.
2 . A method for treating endometriosis in a mammal comprising administering to said mammal a composition comprising IL-17 in an amount effective to alleviate at least one symptom of endometriosis in said mammal.
3 . The method of claim 2 , wherein said IL-17 is administered in an amount effective to inhibit the cellular adhesion of sloughed endometrial tissue to surrounding tissue.
4 . The method of claim 3 , wherein said administration of IL-17 reduces the number of endometrial lesions in said mammal.
5 . The method of claim 1 , further comprising administering an agent that inhibits the production, activity or expression of TNFα or its receptor.
6 . The method of claim 5 , wherein said agent is an anti-TNF antibody or a fragment thereof.
7 . The method of claim 1 or claim 5 , further comprising administering an agent that treats endometriosis.
8 . The method of claim 1 , wherein said composition comprising IL-17 is administered in combination with surgical resection of endometrial tissue.
9 . The method of claim 8 , wherein said composition comprising IL-17 is administered before, after or during said surgical resection.
10 . The method of claim 2 , further comprising administering hormone therapy.
11 . The method of claim 10 , wherein said hormone therapy comprises administering a gonadotropin releasing-hormone (GnRH) agonist.
12 . The method of claim 11 , wherein the GnRH agonist is selected from the group consisting of nafarelin acetate, leuprolide acetate, goserelin acetate, and buserelin acetate.
13 . The method of claim 11 , wherein said composition comprising IL-17 is administered concurrently with said GnRH agonist or is administered upon cessation of GnRH agonist.
14 . The method of claim 11 , further comprising administering to said individual an estrogen agent with a progestin agent to the woman on a daily basis for a period of time sufficient to prevent the symptoms of endometriosis.
15 . The method of claim 14 , wherein the estrogen agent is administered at a level that is biologically equivalent to about 5 to about 35 micrograms of ethinyl estradiol and the progestin agent is biologically equivalent to about 0.2 to about 1.5 milligrams of norethindrone acetate.
16 . The method of claim 15 , wherein the estrogen agent and the progestin agent are coadministered transdermally or orally.
17 . The method of claim 16 , wherein the oral administration of estrogen agent and the progestin agent is as a monophasic tablet or capsule.
18 . A method for promoting decidualization of endometrial stromal cells in a mammal comprising administering to said mammal a composition comprising IL-17 in an amount effective to render the endometrial stromal cells of said mammal receptive to implantation as compared to cells of said mammal prior to administration of said composition.
19 . The method of claim 18 , wherein the promotion of decidualization of said cells is monitored using a characteristic selected from the group consisting of an increase IGFBP-1 expression, an increase in IL-1b expression, activation COX-2 expression, an increase in intracellular cAMP, decreased a-smooth muscle actin expression, an increase in PGE2 production, an increase in prolactin production, an increase in amount of oocyte implantation, and a swelling of endometrial stromal cells in response to said IL-17 administration.
20 . The method of claim 18 , wherein said mammal is suffering from endometriosis and administration of said IL-17 reverses the endometriotic phenotype of the endometrial cells to a phenotype that is receptive to embryo implantation.
21 . A method of screening for an agent that inhibits TNFα-induced endometrial cell adhesion said method comprising:
i) determining the binding of endometrial cells in culture with a solid support in the presence of TNFα;
ii) determining the binding of endometrial cells in culture with a solid support in the presence of TNFα in the presence of IL-17;
iii) determining the binding of endometrial cells in culture with a solid support in the presence of TNFα, IL-17 and a candidate agent; and comparing the binding in step (ii) with step (iii), wherein a decrease in binding between step (ii) and step (iii) indicates that the agent is an inhibitor of TNFα-induced endometrial cell adhesion.
22 . A composition comprising IL-17 for use in the treatment of infertility.
23 . A composition comprising IL-17 for use in the treatment of endometriosis.