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 vivo. 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.