Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide.

Abstract

LPS and peptidoglycan or covalent peptidoglycan-polysaccharide (PG-PS)' complexes are the major toxic components of bacterial cell walls. Lipid A and PG possess many of the biologic activities that LPS and PG-PS, respectively, have in common, such as pyrogenicity, polyclonal activation of lymphoid cells, complement activation, mitogenicity, macrophage activation, and adjuvanticity (1-3). Both also induce arthritis after injection into laboratory animals. Systemic injection of rats with a sterile, aqueous suspension of PG-PS from the group A streptococcus (PG-APS) induces a chronic erosive relapsing arthritis that has many features of rheumatoid arthritis (4-6). Distinct PG-PS structures from a number of other bacteria, including human indigenous intestinal species, induce arthritis of varying chronicity (7-10) . LPS induces primarily an acute arthritis of relatively short duration after intraarticular (i.a.) injection (7, 11-15), but there have been few reports of its arthropathic activity after systemic administration (16, 17, 17a) .In spite of the shared biologic properties and ubiquitous distribution of LPS and PG-PS, the interaction of their phlogistic activities in an inflammatory process has received little attention. During investigations of mechanisms of recurrent arthritis induced by PG-APS, we noted that a systemic injection of 100 Ag of Salmonella typhimurium LPS induced a transient recurrence of arthritis in rat joints previously inflamed by exposure to PG-APS (7,18) . We now report that the systemic injection of a much lower dose of LPS will induce a recurrence of arthritis injoints inflamed 3 wk previously by the intraarticular injection of PG-APS and describe this reaction in detail . We show that LPS from many bacteria, including Yersinia enterocolitica and Neisseria gonorrhoeae, are active ; that lipid A

Interleukin‐1β enhances capsaicin‐induced neurogenic vasodilatation in the rat skin

“…This cytokine is not only a proinflammatory substance (Stimpson et al, 1988;Hom et al, 1992;van de Loo et al, 1992) but can per se induce inflammation and tissue destruction (Pettipher et al, 1986;Chandrasekhar et al, 1990). The finding that intra-articular injection of IL-1 induces release of substance P. presumably from afferent nerve fibres, into the synovial fluid (O'Byrne et al, 1990a,b) suggests that cytokines themselves could evoke signs of neurogenic inflammation.…”

Toll-like Receptor

“…Systemic injection of streptococcal cell wall could induce arthritis, 140 which has been followed by numerous studies using PAMPs to evoke arthritis in animal models. Microbesderived TLR ligands, such as peptideglycan for TLR2, 141 dsRNA via TLR3, 142 LPS for TLR4 143 and CpGDNA for TLR9 144 have frequently been used for to provoke or accelerate experimental arthritis. TLR4 was reported to be involved in the chronicity and erosive destruction of streptococcal cell wall-induced arthritis, which was coincident with the antigenspecific IL-17 response.…”

Flare-up of experimental arthritis in mice with murine recombinant IL-1

“…lung, vitreous tissue and rat ankles [17,27,28], the naive murine knee joint lacked oedema formation in response to IL-I. In general, full blown oedema is often found in the presence of a capillary permeability enhancer and a vasodilator, e.g.…”

“…In rals., pre-and post-treatment wilh IL-1 loeiilly reduced joint swelling and histopathology of antigen-indueed arthritis [ 16). In peptidoglycan-polysaecharide-indueed arthritis in rat ankles, IL-1 induced exacerbations of arthritis, but clearcut clinical and histological differences were only found after repeated lL-l injectionsinto those previously injured joints [17]. Overall, exogenous IL-1 had intricate effects on pathogenesis of experimental arthritis and this may depend on route, site (predisposed) and time of administration.…”