INTERLEUKIN-1 MEDIATES GUINEA-PIG GALLBLADDER INFLAMMATION IN-VIVO

Interleukin-1 (IL-1) is a cytokine with multiple immunologic and infla mmatory properties. We previously demonstrated that lipopolysaccharide (LPS) stimulates release of IL-I, and IL-1 stimulates inflammation in guinea pig gallbladder in vivo. We hypothesized that IL-1 mediates LP S-induced guinea pig gallbladder inflammation in vivo. LPS and IL-1 we re instilled into guinea pig gallbladder lumen alone (with cystic duct ligation) and with IL-1 ra and indomethacin, respectively (n = 4). Wa ter transport across gallbladder mucosa, myeloperoxidase and IL-1 rele ase from gallbladder tissue, and prostaglandin E-2 (PGE(2)) in lumenal fluid were measured. Values for test agents and inhibitory agents wer e compared to saline controls using Student's t test (P < 0.05), Intra lumenal LPS and IL-1 both stimulated gallbladder inflammation. LPS-ind uced and IL-l-induced inflammation were inhibited by both IL-1 ra and indomethacin. LPS stimulated IL-1 release and IL-1 itself caused gallb ladder inflammation. LPS stimulated gallbladder inflammation as manife st by increased myeloperoxidase and PGE(2) release, and water secretio n into the gallbladder lumen. The inflammatory effects of LPS were inh ibited by IL-1 ra. Taken together, these findings indicate that IL-1 i s a mediator of LPS-induced guinea pig gallbladder inflammation in viv o. (C) 1997 Academic Press.