Early cartilage degradation in cationic immune complex arthritis in mice: relative role of interleukin 1, the polymorphonuclear cell (PMN) and PMN elastase.
OBJECTIVE
To determine the relative role of interleukin 1 (IL-1), polymorphonuclear cell (PMN) and PMN elastase in early cartilage degradation in cationic immune complex mediated arthritis (ICA) in mice. ICA is characterized by early production of IL-1, pronounced influx of PMN and marked cartilage degradation within one day.


METHODS
IL-1 was neutralized by polyclonal antibodies against IL-1 alpha and IL-1 beta, given shortly before arthritis induction. The role of PMN was studied in mice made neutropenic by whole body irradiation (750 rad). The effect of elastase was examined in beige mice with PMN deficient in elastase.


RESULTS
Neutralizing IL-1 during arthritis induction reduced PMN infiltration significantly and diminished cartilage degradation by 50%. In neutropenic mice, joint inflammation was virtually absent and cartilage proteoglycan loss was abolished. Finally arthritis was induced in beige mice. Although elastase appeared to be the dominant cartilage degrading factor in vitro, we found no difference in cartilage degradation in arthritic joints of beige mice and their normal littermates.


CONCLUSIONS
Our data suggest that IL-1 is a crucial factor regulating PMN influx in ICA. The PMN are involved in cartilage degradation but a direct destructive role (e.g., by elastase) seems unlikely.
van Lent
P L
PL
Department of Rheumatology, University Hospital, St. Radboud, Nijmegen, The Netherlands.
van den Hoek
A E
AE
van den Bersselaar
L A
LA
van de Loo
F A
FA
Eykholt
H E
HE
Brouwer
W F
WF
van de Putte
L B
LB
van den Berg
W B
WB
D000818:Animals; D001168:Arthritis / Q000209:etiology*; D002358:Cartilage, Articular / Q000473:pathology* / Q000503:physiopathology; D002412:Cations; D004195:Disease Models, Animal; D007105:Immune Complex Diseases / Q000209:etiology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009503:Neutropenia / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000172:deficiency / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism
D002412:Cations; D007375:Interleukin-1; D011509:Proteoglycans; D010196:Pancreatic Elastase