2nd Annual BMRP Investigator Meeting - Abstract

Bromelain Treatment of Inflammatory Bowel Disease

Laura P. Hale^a,, Marcia R. Gottfried and Jane E. Onken

Departments of Pathology and Medicine, Duke University Medical Center (Durham, North Carolina, U.S.A.)

Bromelain is a natural proteinase product that is marketed as a “digestive aid.”  We and others have previously shown that proteolytically active bromelain specifically removes certain cell surface molecules and affects leukocyte migration, activation, and production of cytokines and inflammatory mediators in vitro.  Recently, oral bromelain was anecdotally reported to induce clinical and histologic remission of ulcerative colitis in two patients whose disease was refractory to multi-agent medical therapy.

The purpose of these studies was to determine the potential of bromelain for treatment of colitis, using murine models of inflammatory bowel disease (IBD) as well as in vitro treatment of human colon biopsies.  C57BL/6 IL-10 deficient mice treated orally with bromelain once daily beginning at age 5 weeks developed significantly less colon inflammation than control mice treated with water alone (histologic scores 29 + 15 vs.15 + 7 at 34 weeks; p = 0.04).  In separate experiments, bromelain concentrations within the colon of treated mice were found to be dependent on both dose and formulation.  Stool bromelain activity in mice given bromelain in antacid was sufficient to remove bromelain-sensitive molecules from both leukocytes and colon epithelial cells.  Paired biopsies from the colon of human patients with and without IBD were treated with either bromelain or media and cultured for 24 hours.  Culture supernatants were analyzed for cytokine and chemokine production using multiplex fluorescent immunoassays.  Bromelain treatment of biopsies from IBD patients decreased production of several pro-inflammatory cytokines and chemokines, including TNF-a, IL-1b, and IFN-g.  These changes would be predicted to decrease inflammatory activity in vivo.

Taken together, these studies confirm the potential of bromelain in the therapy of colitis.  The use of oral proteinases to locally modify inflammation in the gut deserves continued study as a potential new therapy for IBD.

^aPrincipal Investigator