Recombinant human
interleukin (rhIL)-11 has anti-inflammatory and protective effects in models of intestinal mucosal injury. Our aim was to investigate whether oral treatment with
rhIL-11 reverses functional abnormalities in intestinal muscle contractility resulting from
human leukocyte antigen (HLA)-B27-dependent gut
inflammation. Isometric contractions were studied in jejunal and colonic longitudinal muscles. Muscle strips were isolated from
HLA-B27 transgenic rats with spontaneous
inflammation following treatment with enteric-coated
rhIL-11 multiparticulates (500 microg/kg) or placebo multiparticulates given orally every 48 h for 2 weeks.
Myeloperoxidase (MPO) activity was measured in intestinal tissue samples and served as an index of
inflammation. Colonic damage was also assessed histologically. The
HLA-B27 rats receiving placebo had chronic
diarrhea, and MPO activity was increased in the jejunum and colon. Intestinal
inflammation was associated with a decreased ability of the muscles to generate active tension in response to electrical field stimulation,
carbachol, or high KCl. In the jejunum of placebo-treated
HLA-B27 rats, concentration-effect curves for
carbachol were shifted to lower concentrations yielding a higher EC50. Oral treatment of
HLA-B27 rats with
rhIL-11 suppressed the symptoms of
diarrhea, normalized MPO activity, and improved the colonic damage score. Simultaneously, neurally mediated responses were improved and the maximal tension generated by
carbachol or KCl was normalized in the jejunum and colon. The EC50 for
carbachol in the jejunum of
HLA-B27 rats was also normalized by
rhIL-11 treatment. Our data demonstrate that
oral administration of enteric-coated
rhIL-11 suppresses intestinal
inflammation and reverses intestinal smooth muscle dysfunction in
HLA-B27 transgenic rats.