Inflammatory disease models

Vice versa, the disease may affect the immunogenicity of biopharmaceuticals. For instance, the activated immune system in diseases like rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease is likely to produce a faster and/or stronger response to biopharmaceuticals. Inasmuch as this applies to patients, the same issue may have relevance for safety testing that is, application of a relevant inflammatory disease model may give greater insight and better predictability than healthy animals do. 

In a more recent publication, Dompe discussed their efforts to identify follow-up compounds that produce more favorable PK characteristics than reparixin [132]. One such compound is trifluoromethanesulfonate 44, which inhibited both CXCL8- and CXCLl-induced PMN chemotaxis with equal potencies (IC50 8.4 and 26 nM, respectively) [133] and in addition gave excellent rat PK properties Cl 4.1 mlmin kg , P 72%) [134]. Extensive in vivo profiling showed 44 to be orally efficacious in a range of inflammatory disease models such as the rat adjuvant-induced arthritis model. 

Resolvins (Rv) are derivatives of EPA and/or DHA and are now well-established as exhibiting anti-inflammatory or pro-resolving properties. They were first identi-hed in a murine air pouch model by Serhan in 2000 (Serhan et al. 2000), and since then have been both applied and detected in various animal inflammatory disease models (i.e., colitis, ischemia-reperfusion injury, wound healing) and human nutritional intervention/disease studies (Kasuga et al. 2008 Bento et al. 2011 Norling et al. 2011 Giera et al. 2012 Mas et al. 2012). 

In addition to the NOD mouse, Entelos has models for several human metabolic diseases (diabetes, obesity, and metabolic syndrome), inflammatory diseases (rheumatoid arthritis), and respiratory diseases (asthma and COPD). 

Human leukocyte elastase is a protease that degrades elastin and other connective tissue components. It is implicated in the pathogenesis of pulmonary emphysema and other inflammatory diseases such as rheumatoid arthritis and cystic fibrosis. Porcine pancreatic elastase has often been used as a model for HLE. Both enzymes have a small primary binding site Si. 

As a consequence of their immunosuppressive activity, Tregs may function as a cellular therapeutic agent that ameliorates allergies and autoimmune diseases. This has been proven in several disease models including asthma, inflammatory bowel disease, multiple sclerosis and CHS reactions. Others and we have studied the effects of in vivo applied Tregs as a possible therapeutical means to curb... 

Many animal models have been described in which inflammation is induced and activation of the endothehum occurs. Here, some disease-specific models, in addition to some general inflammatory experimental models will be summarized. 

The histamine H4-receptor which was discovered in 2001 has been shown to have a role in chemo-taxis and mediator release in various types of immune cells including mast cells, eosinophils, dendritic cells and T cells. H4-receptor antagonists have been shown to have anti-inflammatory properties and efficacy in a number of disease models, such as those for asthma and colitis in vivo. Cinnarizine has a high affinity for the H4-receptor. Recently other H4-receptor antagonists have been developed with high receptor affinity and specificity. The first few studies into the function of H4-receptors suggested... 

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