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

Intra-articular injections of murine recombinant IL-1 (mrIL-1) during the chronic phase of antigen-induced arthritis (AIA) induced a flare-up of the smouldering inflammation. The exacerbation was characterized by acute and transient joint swelling and this coincided with the extravascular accumulation of neutrophils. IL-1 injected into arthritic joints of neutropenic mice demonstrated that joint swelling was independent of the neutrophil influx into the joint. Both phenomena were absent when IL-1 was injected into a naive joint. The IL-1-induced flare-up was not T cell mediated as in the antigen-induced flare-up, and suggestive evidence is presented that IL-1 sensitivity depended on the resident macrophage population. This explained why the hypersensitivity is not restricted to the immunologically mediated arthritis but reflects a more general hypersensitivity of previously injured joints, e.g. zymosan-induced arthritis and IL-1-affected joints. In addition, IL-1 could also potentiate the antigen-specific flare-up of chronic AIA and prolongs the duration of the exacerbation. Our data indicate that joints bearing a chronic infiltrate are at risk from exacerbations in two ways: a T cell mediated rechallenge with antigen, and a non-specific reactivation by systemic and local IL-1 generation.