Immune complexes, but not streptococcal cell walls off zymosan, cause chronic arthritis in mouse strains susceptible for collagen type II auto-immunearthritis

In this study we investigated mechanisms involved in the chronic character of experimental collagen type a induced arthritis (CLA). We compared tbe kn ee joints of mouse strains which are prone to develop this autoimmune disea se (DBA/1,B10RIII) with other nonsusceptible mouse strains (C57Bl/6,BALB/c) in their reaction to different stimuli: immune complexes OC), zymosan and streptococcal cell waals (SCW). Inflammation was evaluated bg Tc-99m uptake measurements and in haematoxylin- and eosin-stained knee-joint sections. P assively induced immune complex mediated arthritis (ICA) in knee joints of C57Bl/6 and BALB/c mice, showed moderate cell influx at day 3, whereas at d ay 7 only minor amounts of inflammatory cells were observed. In contrast, i n arthritic DBA/1 and, to a lesser extent, in B10.RIII joints, a tremendous cell influx was observed at day 3 and even at day 14 there was still signi ficant synovitis. In contrast, if arthritis was elicited by intra-articular injection of zymosan or SCW in C57Bl/6 and DBA/1, the course of inflammati on was similar in both strains and no chronic inflammation developed, In li ne with severe arthritis, chemotactic factor production was dramatically en hanced in ICA in DBA/1 mice, and a prolonged production of IL-1 was evident . When IL-1 was neutralized before or during the ICA using specific anti-IL -1 alpha,beta, antibodies, inflammation could be blocked completely. Single or multiple injection of IL-1 In the knee joint of C57Bl/6 or DBA/1 showed comparable inflammation, indicating that the chemotactic response per se i s comparable in both strains. No prolonged production of LL-I was found dur ing zymosan or SCW arthritis. Selective removal of macrophages from the syn ovial intima prior to ICA induction (using clodronate-containing liposomes) prevented the onset of inflammation in C57Bl/6 and DBA/1 mice. It can be c oncluded that immune complexes, but not zymosan or SCW, cause a more severe and chronic arthritis in mouse strains which are susceptible for collagen type IT autoimmune arthritis. This is due to higher and prolonged expressio n of IL-1 and chemotactic factors, caused by stimulation with immune comple xes. The interaction of IC with lining macrophages probably plays a dominan t role in development of chronicity. (C) 1999 Academic Press.