Molecular and cellular mediators of interleukin-1-dependent acute inflammatory arthritis.
OBJECTIVE
To examine the molecular and cellular mechanisms in a model of acute inflammatory monarticular arthritis induced by methylated bovine serum albumin (mBSA) and interleukin-1 (IL-1).


METHODS
Mice were injected intraarticularly with mBSA on day 0 and subcutaneously with recombinant human IL-1beta on days 0-2. At day 7, knee joints were removed and assessed histologically. Flow cytometry and RNase protection were used to analyze IL-1-dependent events.


RESULTS
C57BL/6 (B6), 129/Sv, and (B6 x 129/ Sv)F1 hybrid mice, all H-2b strains, were susceptible to mBSA/IL-1-induced arthritis, whereas C3H/HeJ (H-2k) mice were not. B6 mice lacking T and B cells (RAG1-/-) or major histocompatibility complex (MHC) class II antigens (MHCII-/-), and B6 mice treated with a CD4+ T cell-depleting monoclonal antibody, were resistant to disease. In contrast, B cell-deficient (muMT/ muMT) mice developed arthritis at an incidence and severity similar to that of controls. RelB-deficient (RelB-/-) bone marrow chimeric mice had arthritis that was significantly reduced in incidence and severity. In B6 mice, flow cytometry demonstrated an IL-1-dependent leukocyte infiltration into the synovial compartment and RNase protection assays revealed induction of messenger RNA (mRNA) for the chemokines monocyte chemoattractant protein 1, macrophage inhibitory protein 2 (MIP-2), RANTES, MIP-1alpha, and MIP-1beta, in vivo and in vitro.


CONCLUSIONS
Arthritis induced by mBSA/IL-1 is strain specific and dependent on CD4+ T lymphocytes and at least partially on RelB, but not on B lymphocytes or antibody. IL-1 contributes to leukocyte recruitment to the synovium and directly induces chemokine mRNA production by synovial cells. This model of acute monarticular arthritis is particularly suitable for further investigations into cell-mediated immunity in arthritis and the role of IL-1.
Lawlor
K E
KE
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Campbell
I K
IK
O'Donnell
K
K
Wu
L
L
Wicks
I P
IP
D000208:Acute Disease; D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013045:Species Specificity; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis
D018925:Chemokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497594:Relb protein, mouse; D014157:Transcription Factors; C029180:methylated bovine serum albumin; D051841:Transcription Factor RelB; D012710:Serum Albumin, Bovine