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.
van de Loo
A A
AA
Department of Rheumatology, University Hospital St. Radbound, Nijmegen, The Netherlands.
Arntz
O J
OJ
van den Berg
W B
WB
D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000276:immunology; D001168:Arthritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D003208:Concanavalin A / Q000008:administration & dosage; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007596:Joints / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011453:Prostaglandins / Q000502:physiology; D013997:Time Factors
D000941:Antigens; D007375:Interleukin-1; D011453:Prostaglandins; D003208:Concanavalin A; D007213:Indomethacin