Anti Inflammatory/Effects of CRF Binding Protein

CRF, a 4l-amino acid peptide, plays a significant role in modulating inflammatory responses throughcoordinated actions in the nervous, endocrine and immune systems. CRF has indirect anti-inflammatorystimulation of the pituitary- adrenocortical axis resulting in glucocorticoid secretion. In additionclinical data suggest important autocrine/paracrine pro-inflammatory roles for CRF in arthritis. Thuand/or block the effects of local overproduction of CRF at inflammatory sites may represent novel agof rheumatoid arthritis and other inflammatory conditions. A circulating form of a human binding profor CRF and the ability to inactivate CRF has been recently purified and cloned. The studies of theevaluating the potential anti-inflammatory effects of the human CRF-BP. The efficacy of CRF- BP willrat models of acute inflammation (carrageenin- and oyster-glycogen induced inflammation) and in twoarthritis (streptococcal cell wall- and adjuvant-induced arthritis). The study will also include pilout the best methodology for recombinant expression and purification of scale-up quantities of the Cthe development of assay systems for detection of immunoreactive and biologically active forms of thprotein. The second phase of the study will involve clinical studies to evaluate the anti-inflammatobinding protein in rheumatoid arthritis patients. In addition, orally active, small molecule non-pepantagonists will be identified as second generation agents for the treatment of rheumatoid arthritis