dual integrin alpha-V/beta-1/alpha-V/beta-6 inhibitors (Morphic Therapeutic)

Oromucosal (o.m.) administration of interferon-alpha (IFN-alpha) during either allergic sensitization (days 0-6) or the hypersensitive response (days 11 and 12) or both periods caused a dose-dependent reduction in allergen-specific IgE production and allergen-induced eosinophil recruitment in mice sensitized to ragweed pollen, a common allergen in humans. Treatment during the hypersensitive response period alone appeared to be most effective. Oromucosal treatment was as effective as intraperitoneal (i.p.) treatment, with maximum inhibition of both allergen-specific IgE production and allergen-induced eosinophil recruitment observed at a dose of a 1000 IU IFN-alpha. Treatment of animals with up to 10(5) IU murine IFN-alpha/beta (MuIFN-alpha/beta) by either the om. or i.p. route did not inhibit significantly allergen-specific IgG production, which may even have been increased at certain doses of IFN. Treatment of animals with up to 10(5) IU MuIFN-alpha/beta by either the o.m. or i.p. route did not affect significantly total serum IgE or IgG levels. Oromucosal administration of IFN-alpha reduced allergen-specific IgE production and allergen-induced eosinophil recruitment in the absence of detectable toxicity, the induction of H(2) antigen expression, and 2',5'-oligoadenylate synthetase activity associated with parenteral administration of IFN-alpha and thus may find application for the treatment of asthma and associated viral infections.

Since vascular resistance is elevated in hypertension, it is suggested that vasodilators lower the blood pressure by a physiologic mechanism and therefore must be more useful than cardiac output-lowering drugs. This is not entirely correct. Drugs that lower cardiac output are also relative vasodilators, but the vasodilation occurs at a lower level of cardiac output. It is also not necessarily true that all vasodilators are good antihypertensive agents. The clinical profile of a vasodilator depends on its effect on the venous return, cardiac output, regional blood flow, renin-angiotensin system, and sympathetic reflexes. From the viewpoint of hemodynamics, an ideal antihypertensive drug is a vasodilator that does not excessively increase cardiac output, causes no fluid retention, does not induce a great deal of venodilation, and does not elicit substantial neurohumoral counterregulation. Angiotensin-converting-enzyme inhibitors, some calcium antagonists, and some combined alpha/beta-blocking agents come close to satisfying the hemodynamic definition of an ideal antihypertensive drug.