This open-label trial of G-CSF in Crohn's disease seeks to establish the safety and study the efficacy of this drug to induce remission in moderately active disease. We have screened 23 and enrolled 12 subjects in this protocol to date. Responses have ranged from complete remission to no response at all. We are accruing data on changes in cytokine secretion by peripheral and lamina propria mononuclear cells and dendritic cell populations. We are correlating these with clinical parameters including biochemical markers of gut inflammation. The higher dose cohort has now begun enrollment and oour plans are to double the treatment period based upon our current data of response dependent on duration of induced changes in dendritic cell populations. The major scientific advance has been the correlation of induction of Th2 and regulatory cytokines with clinical improvement in patients with active Crohn's disease. G-CSF represents a novel approach to Crohn's disease therapy as a true immunomodulator rather than immunosuppressant or blocker of inflammatory mediators. This advance fills a gap in the knowledge of how the mucosal cytokine milieu can affect the clinical expression of Crohn's disease. In addition this advance directs future research to look at other candidate therapeutic targets involved in the G-CSF response, provides a basis for characterizing a patient phenotype which correlates with novel disease susceptibility genes, and provides a rational for integrating this therapy with other complementary agents and for use in maintaining disease remission.
| Fuss, Ivan J; Heller, Frank; Boirivant, Monica et al. (2004) Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 113:1490-7 |
