University of Virginia Health System

Research Interest: Cytokine Network and Mucosal Immunity

The focus of our laboratory is the investigation of the cytokine network in the regulation of mucosal immune responses and its alteration in association with intestinal inflammation. We use a comprehensive approach, including state-of-the-art molecular biology techniques, animal models of inflammation, and cultured human intestinal mucosal cells. Using these methodologies, our group has demonstrated the critical role of the IL-1ra/IL-1 system in inflammatory diseases, specifically in inflammatory bowel disease (IBD). Our laboratory was the first to demonstrate that specific in vivo blockade of IL- 1 effectively reduced the severity of inflammation in an animal model of inflammatory disease. Additionally, we have reported an intrinsic imbalance in the relative concentration of proinflammatory IL-1 and antiinflammatory IL-1ra in patients with IBD, which may be responsible for the chronic, relapsing clinical course of the disease. More recently, our search for the genetic mechanism(s) underlying these findings has involved studies investigating the association and functional significance of novel cytokine polymorphisms, particularly in the IL-1 gene cluster, and chronic inflammatory diseases. A major goal of these studies is to understand the molecular mechanism(s) of intestinal inflammation and to develop novel therapeutic modalities for patients affected by chronic inflammatory diseases.

Dr. Cominelli is also a member of the Beirne B. Carter Center for Immunology Research.

Selected Publications:

Casini-Raggi V., L. Monsacchi, K. Vosbeck, C.C. Nast, T.T. Pizarro, F. Cominelli. (1995). Antiinflammatory effects of CGP 47969A, a novel inhibitor of proinflammatory cytokine synthesis, in rabbit immune colitis. Gastroenterology. 109:812-8.

Casini-Raggi V., L. Kam, Y.J.T. Chong, C. Fiocchi, T.T. Pizarro, F. Cominelli. (1995). Mucosal imbalance of interleukin-1 and interleukin-1 receptor antagonists in inflammatory bowel disease: A novel mechanism of chronic intestinal inflammation. J. Immunol. 154:2434-40.

Ferretti, M., V. Casini-Raggi, C.C. Nast, S.P. Eisenberg, T.T. Pizarro, F. Cominelli. (1994). Neutralization of interleukin-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis. J. Clin. Invest. 94:449-53.

Cominelli F., M. Bortolami, T.T. Pizarro, L. Monsacchi, M. Ferretti, M.T. Brewer, S.P. Eisenberg, R.K. Ng. (1994). Rabbit interleukin-1 receptor antagonist: Cloning, expression, functional characterization and regulation during intestinal inflammation. J. Biol. Chem. 269:6962-71.

Cominelli, F., C.C. Nast, B.D. Clark, R. Shindler, R. Llerena, V.E. Eysselein, C.A. Dinarello. (1990). Interleukin-1 gene expression, production and effect of specific receptor blockade in rabbit immune colitis. J. Clin. Invest. 86:972-980.