In vivo administration with IL-1 accelerates the development of collagen-induced arthritis in mice.
In an attempt to examine the in vivo proinflammatory properties of IL-1, the effects of rIL-1 beta on the development of collagen-induced arthritis in mice were investigated. The results presented in this paper demonstrated that the administration of rIL-1 beta via mini-osmotic pumps into DBA/1 mice which were suboptimally immunized with native chick type II collagen (NcII) markedly accelerated the onset as well as the progression of the arthritic disease. When IL-1-containing osmotic pumps were s.c. implanted onto mice 18 days post-collagen immunization, clinical signs of arthritis appeared within 3 to 4 days after the implant with the pumps. Maximal incidence of arthritis which was usually 80 to 100% occurred between the 6th and 7th day after the administration of rIL-1 beta. Histologic analyses revealed that the knee and ankle joints from mice which were treated with rIL-1 beta for 7 days were most severely and consistently affected. Furthermore, these IL-1-treated mice exhibited granulocytic hyperplasia within the marrow as well as marked peripheral blood neutrophilia. By contrast, arthritis was not observed during the 7-day course of the IL-1 study in the following control groups: 1) mice that were only immunized with NcII, and 2) collagen-immunized mice which received osmotic pumps containing PBS. A substantial number of these collagen-immunized mice which were not treated with IL-1 eventually developed arthritis but at later times after the incidence of arthritis had peaked in the IL-1-treated group. In addition, unimmunized mice failed to develop arthritis upon treatments with IL-1 beta. Moreover, the humoral responses to NcII were not altered in the IL-1-treated mice. Thus, these in vivo studies suggest that IL-1 is potentially capable of triggering the various inflammatory events of collagen-induced arthritis, and thereby, contribute to the pathogenesis of murine arthritis.
Hom
J T
JT
Department of Immunology, Lilly Research Laboratories, Indianapolis, IN 46285.
Bendele
A M
AM
Carlson
D G
DG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001168:Arthritis / Q000209:etiology*; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D003094:Collagen / Q000276:immunology; D007375:Interleukin-1 / Q000008:administration & dosage*; D007964:Leukocytosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D007375:Interleukin-1; D011994:Recombinant Proteins; D003094:Collagen