DIFFERENT ROLES OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 IN MURINE STREPTOCOCCAL CELL-WALL ARTHRITIS

In this study two different aspects of tumour necrosis factor alpha (T NF-alpha) and interleukin 1 (IL-1) in locally induced murine streptoco ccal cell wall arthritis (SCW) were investigated. First, the kinetics and interdependence of TNF-alpha and IL-1 release; and second, their i nvolvement in inflammation and cartilage destruction. Kinetic studies showed that the TNF-alpha peak level preceded the IL-1 peak level. How ever, in vivo neutralization of TNF-alpha did not result in decreased IL-1 bioactivity or immunoreactivity, suggesting that there is no domi nant TNF-alpha-dependent TL-1 release in this model. Inflammation was studied by measuring knee joint swelling and inflammatory cell influx. Impact on cartilage was studied by measuring chondrocyte proteoglycan synthesis and cartilage proteoglycan depletion. The role of TNF-alpha in these phenomena was investigated using anti-TNF-alpha antibodies a nd tumour necrosis factor binding protein (TNFbp), Similarly, the role of IL-1 was studied using anti-IL-1 antibodies or IL-1 receptor antag onist (IL-1Ra). Anti-TNF-alpha treatment significantly reduced joint s welling, whereas this effect was not found using anti-IL-1 or IL-1Ra. In contrast, neutralization of IL-1, but not TNF-alpha, resulted in a significant decrease of chondrocyte proteoglycan synthesis inhibition. Moreover, histology revealed that anti-IL-1 treatment reduced cartila ge proteoglycan depletion and inflammatory cell influx. Combined anti- TNF-alpha/anti-IL-1 treatment significantly suppressed both inflammati on and cartilage damage. However, the impact on these separate paramet ers did not exceed the effects of either anti-TNF-alpha. or anti-IL-1. It can be concluded that both TNF-alpha and IL-1 exert specific activ ities in SCW arthritis. The involvement of TNF-alpha in this model is limited to joint swelling, whereas IL-1 plays a dominant role in carti lage destruction and inflammatory cell influx. (C) 1998 Academic Press .