Interleukin-1 mediates guinea pig gallbladder inflammation in vivo

Interleukin-1 (IL-1) is a cytokine with multiple immunologic and inflammatory properties. We previously demonstrated that lipopolysaccharide (LPS) stimulates release of IL-1, and IL-1 stimulates inflammation in guinea pig gallbladder in vivo. We hypothesized that IL-1 mediates LPS-induced guinea pig gallbladder inflammation in vive. LPS and IL-1 were instilled into guinea pig gallbladder lumen alone (with cystic duct ligation) and with IL-1 ra and indomethacin, respectively (n = 4). Water transport across gallbladder mucosa, myeloperoxidase and IL-1 release from gallbladder tissue, and prostaglandin E₂ (PGE₂) in lumenal fluid were measured. Values for test agents and inhibitory agents were compared to saline controls using Student's t test (P < 0.05). Intralumenal LPS and IL-1 both stimulated gallbladder inflammation. LPS-induced and IL-1-induced inflammation were inhibited by both IL-1 ra and indomethacin. LPS stimulated IL-1 release and IL-1 itself caused gallbladder inflammation. LPS stimulated gallbladder inflammation as manifest by increased myeloperoxidase and PGE₂ release, and water secretion into the gallbladder lumen. The inflammatory effects of LPS were inhibited by IL-1 ra. Taken together, these findings indicate that IL-1 is a mediator of LPS-induced guinea pig gallbladder inflammation in vivo.