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Concerning pharmacological characterization of drugs which may be effective in the treatment of COPD, just as there is no single animal model, we must also remember that no single drug has provided consistent efficacy in the clinical treatment of the disease. Therefore, a potential therapeutic drug regimen must be assessed in a model which appropriately reflects a particular aspect of the disease (i.e., inflammatory cell infiltration, mucus hypersecretion, airway wall remodeling, emphysema, and systemic disease). Because some agents (agonists, inhibitors or antagonists) may work in only certain animals, the appropriate stimulus and the particular therapeutic drug standard to which it should be compared may be species and strain dependent. Therefore, whenever possible, careful or coordination and comparison of the activity found in tissues from the species and models selected to healthy and diseased human tissues should be made. Although rational therapeutic approaches based on inhibitory activity in a number of these models may increase the level of confidence in finding efficacy in the disease state, one should not oversimplify the etiology of the disease to fit the overall profile of the drug.

Concerning pharmacological characterization of drugs which may be effective in the treatment of COPD, just as there is no single animal model, we must also remember that no single drug has provided consistent efficacy in the clinical treatment of the disease. Therefore, a potential therapeutic drug regimen must be assessed in a model which appropriately reflects a particular aspect of the disease (i.e., inflammatory cell infiltration, mucus hypersecretion, airway wall remodeling, emphysema, and systemic disease). Because some agents (agonists, inhibitors or antagonists) may work in only certain animals, the appropriate stimulus and the particular therapeutic drug standard to which it should be compared may be species and strain dependent. Therefore, whenever possible, careful or coordination and comparison of the activity found in tissues from the species and models selected to healthy and diseased human tissues should be made. Although rational therapeutic approaches based on inhibitory activity in a number of these models may increase the level of confidence in finding efficacy in the disease state, one should not oversimplify the etiology of the disease to fit the overall profile of the drug.

Concerning pharmacological characterization of drugs which may be effective in the treatment of COPD, just as there is no single animal model, we must also remember that no single drug has provided consistent efficacy in the clinical treatment of the disease. Therefore, a potential therapeutic drug regimen must be assessed in a model which appropriately reflects a particular aspect of the disease (i.e., inflammatory cell infiltration, mucus hypersecretion, airway wall remodeling, emphysema, and systemic disease). Because some agents (agonists, inhibitors or antagonists) may work in only certain animals, the appropriate stimulus and the particular therapeutic drug standard to which it should be compared may be species and strain dependent. Therefore, whenever possible, careful or coordination and comparison of the activity found in tissues from the species and models selected to healthy and diseased human tissues should be made. Although rational therapeutic approaches based on inhibitory activity in a number of these models may increase the level of confidence in finding efficacy in the disease state, one should not oversimplify the etiology of the disease to fit the overall profile of the drug.

Experience in IBD animal modeling has shown us that an ideal animal model cannot be achieved, as the human disease is chronic, unrelenting with multiple remissions and relapses. Despite this shortcoming, the number of animal models of inflammation that relatively mimic IBD either naturally, spontaneously or phenotypically through experimental physical, immunological or genetic manipulations has significantly increased. Many of these models have helped us dissect and substantially advance our understandings of the pathogenesis of IBD, at the same time as providing an unprecedented opportunity for identifying targets for therapeutic intervention and prevention strategies. Since so many experimental animal models are now available, investigators must take into consideration the species, strains, substrains, the microenvironment in which they live and the mediators involved in each of these models, for application to preclinical testing to manipulate the immune system or to develop vaccines or gene therapy.

As inflammation is becoming increasingly viewed as a major and independent risk factor for cardiovascular disease, longstanding models of atherosclerosis and vascular injury must now be evaluated in the context of those pathological features that develop in response to inflammation. It is quite possible that our understanding of existing therapies is about to change dramatically, when the concept of vascular inflammation is overlaid onto the progression of cardiovascular disease. Perhaps an agent as old as aspirin with its bona fide benefit in cardiovascular disease will experience a shift in the attribution of its pharmacological effects, where the anti-inflammatory effects become equally important for cardiovascular disease as the effects on platelet cyclooxygenase.

For preclinical models to be of predictive value in human disease, there must be reasonable parity of biological pathways between man and lower vertebrates. Such may be the case with elements of biology that are highly homologous across mammalian species such as norepinehrine and adrenergic receptors or heparin and anticoagulation, where strong ties have been established between preclinical and clinical pharmacology. The inflammatory process and the immune system operate in a very complex system of activating and attenuating signals, many of which are biologicals that are only partially understood or have yet to be discovered. Further, the parity between the inflammation and immune pathways between man and preclinically tested species may not be as strong as in other areas of biology. While the contribution of inflammation to vascular disease has been recognized, our ability to thoroughly understand its contribution is currently hindered, but no doubt will improve as technology improves.