Methods for relieving asthma-associated airway hyperresponsiveness
Molecules that interact with the NKT cell antigen receptor and its counterpart antigen presenting molecule, but which inhibit the NKT cell immune function, are administered to a patient. Conditions of particular interest include the treatment of systemic lupus erythematosus (SLE), cancer, atherosclerosis, and allergic disease. In some embodiment of the invention, the inhibitory agent is an anergizing glycolipid, for example β-galactosylceramide. Pharmaceutical formulations of such glycolipids are provided, and find use in the treatment of diseases involving undesirable NKT cell activation.
1. A method for relieving asthma-associated airway hyperresponsiveness (AHR) in a patient, comprising: administering to the patient an effective dose of an anti-CD1d antibody, wherein the anti-CD1d antibody relieves asthma-associated AHR in the patient.
2. A method according to claim 1 , further comprising detecting activated NKT cells in a sample obtained from the patient.
3. A method according to claim 2 , further comprising detecting the presence of one or more of (i) eosinophils, (ii) mast cells, (iii) basophils, (iv) CD25 + T lymphocytes, (v) CD4 + T lymphocytes or (vi) neutrophils in the sample.
4. A method according to claim 2 , wherein the activated NKT cells are detected by a proliferation assay, cytokine release assay or NKT cell cytotoxic assay.
5. A method according to claim 2 , wherein the activated NKT cells are detected by measuring IFN-γ and/or IL-4 secretion of activated NKT cells.
6. A method according to claim 2 , wherein the sample is obtained from the lung or serum.
7. A method according to claim 6 , wherein the lung sample is a sputum or BAL sample.
8. A method according to claim 1 , wherein the anti-CD1d antibody is administered locally or systemically.
9. A method according to claim 8 , wherein local administration comprises inhalation or insufflation.
10. A method according to claim 8 , wherein systemic administration comprises intramuscular, intravenous, subcutaneous, peritoneal, local injection, oral, transmucosal, transdermal, or intranasal administration.
11. A method according to claim 1 , further comprising measuring pulmonary airflow obstruction in the patient, wherein a change in flow relative to a patient to which an anti-CD1d antibody has not been administered is determinative of impaired lung function.
12. A method according to claim 1 , wherein the patient is a human being.