Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1994-04-14
1998-06-23
MacMillan, Keith
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
536 27, 536 2351, 536 2431, 435320, 435235, 435240, 435252, 435255, 330387, 530399, 530351, C12P 2102, C12N 1500, C07H 1900
Patent
active
057704015
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to methods and compositions for treating allergic reactions, and, more particularly, for treating bronchial asthma, rhinitis, rhinoconjunctivitis, conjunctivitis, and dermatitis.
BACKGROUND OF THE INVENTION
An allergic reaction is any abnormal or altered reaction to an antigen (or "allergen"). Typically such a reaction is characterized by hypersensitivity of the body to specific substances, whether protein, lipid or carbohydrate in nature. Allergic reactions may be local, e.g. contact dermatitis, or systemic, e.g. anaphylaxis.
Among allergic diseases, bronchial asthma is one of the most significant. In most urban hospitals, it is the leading cause of admission of children. Current medical practice accepts asthma in afflicted individuals to be an unavoidable, incurable illness. While suppression of symptoms is achieved to a degree sufficient to avoid death, urgent medical visits, disturbed sleep, and days lost from work are typically unavoidable.
The disease is generally associated with dyspnea, wheezing, and cough, as well as reversible airway obstruction and airway hyperreactivity to nonspecific stimuli. These responses have been observed in two phases, early and late (Lemanske, Jr., R. F. and M. A. Kaliner, In: Allergy, Principles & Practice (3rd Ed.) pp. 224-246 (1988). See also Kaliner, M. A., Hosp. Prac. 22:73 (1987); Larsen, G., Hosp. Prac. 23:113 (1987)).
Inhalation of allergens by sensitized subjects typically results in an early phase response characterized by bronchoconstriction within 10 minutes of inhalation, reaching a maximum within 1 to 2 hours. In some subjects, the airway narrowing recurs after 3 to 4 hours (i.e. a late phase response), reaching a maximum during the next few hours (O'Byrne, P. M. et al., Am. Rev. Respir. Dis. 136:740 (1987)). This late phase reaction is thought to be due to the cellular phase of inflammation (Hargreave, F. E. et al., Eur. J. Respir. Dis. 69(Suppl 147):16 (1986); O'Byrne, P. M., Chest 90:575 (1986); Dolovich, J. et al., J. Allergy Clin. Immunol. 83(Suppl):521 (1987)).
No complete, long-lasting remissions of asthma have been described in response to any existing therapeutic strategies. For example, systemically administered glucocorticosteroids are potent antiasthmatics; however, the symptoms of the disease are only temporarily suppressed and this is at the cost of well-known side effects, including osteoporosis, weight gain, hypertension, and diabetes (Barnes, P. J., New Eng. J. Med. 321:1517 (1989)). Inhaled steroid therapy also has complications (See Toogood, J. H., J. Allergy Clin. Immunol. 83(Suppl):528 (1987)). Low-dose methotrexate has been offered as a substitute to steroids, particularly for patients for whom the side-effects of steroids are the most devastating (Mullarkey, M. F., New Eng. J. Med. 318:603 (1988)). However, methotrexate, while frequently substituting for toxic doses of corticosteroids, has significant inherent toxicity. Furthermore, it does not eliminate the need for periodic corticosteroids.
There is a great need for new approaches to treatment of allergic disease. Specifically, there is a need for therapy that produces long-lasting anti-inflammatory effect without harm to the patient.
DISCLOSURE OF THE INVENTION
The present invention relates to methods and compositions for treating allergic reactions, including cutaneous, ocular, nasal, gastrointestinal and bronchial allergic disease.
In accordance with the present invention, at least one member selected from the group consisting of Interleukin-1 (IL-1) receptors, Tumor Necrosis Factor (TNF) receptors, and receptor analogues thereof which bind the respective effector, is selectively employed to treat allergic reactions. The present treatment is expected to have many of the beneficial effects of corticosteroids--however, without the toxicity associated with these agents.
One aspect of the present invention contemplates using soluble IL-1 receptors to treat inflammation in tissues. In certain embodiments, this method comprises cont
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MacMillan Keith
Weseman, Esq. James C.
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