Different roles of tumour necrosis factor alpha and interleukin 1 in murine streptococcal cell wall arthritis.

In this study two different aspects of tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) in locally induced murine streptococcal cell wall arthritis (SCW) were investigated. First, the kinetics and interdependence of TNF-alpha and IL-1 release; and second; their involvement in inflammation and cartilage destruction. Kinetic studies showed that the TNF-alpha peak level preceded the IL-1 peak level. However, in vivo neutralization of TNF-alpha did not result in decreased IL-1 bioactivity or immunoreactivity, suggesting that there is no dominant TNF-alpha-dependent IL-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 and tumour necrosis factor binding protein (TNFbp). Similarly, the role of IL-1 was studied using anti-IL-1 antibodies or IL-1 receptor antagonist (IL-1Ra). Anti-TNF-alpha treatment significantly reduced joint swelling, whereas this effect was not found by 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 cartilage proteoglycan depletion and inflammatory cell influx. Combined anti-TNF-alpha/anti-IL-1 treatment significantly suppressed both inflammation and cartilage damage. However, the impact on these separate parameters did not exceed the effects of either anti-TNF-alpha or anti-TNF-1. It can be concluded that both TNF-alpha and IL-1 exert specific activities in SCW arthritis. The involvement of TNF-alpha in this model is limited to joint swelling, whereas IL-1 plays a dominant role in cartilage destruction and inflammatory cell influx. Copyright 1998 Academic Press.