Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1.
Leukocyte adhesion receptors on endothelial cells play an important role in the evolution of synovitis. We studied sequential synovial biopsies at Weeks 0, 2 and 12 in 11 patients with rheumatoid arthritis beginning parenteral gold therapy either alone or combined with 120 mg intramuscular methylprednisolone acetate at Weeks 0, 4 and 8 of treatment. Expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) decreased on synovial blood vessels after both 2 and 12 weeks treatment (p less than 0.05), while the overall vascularity of the synovium did not change. Neutrophil numbers within the synovial membrane also decreased although this did not reach statistical significance. In contrast, there was no significant change in numbers or subset distribution of T cells or in Class II MHC expression by synovial lining cells, mononuclear cells or endothelial cells. Our results suggest that one of the early effects of intramuscular gold and glucocorticoid therapy may be a downregulation of the acute inflammatory process associated with the endothelial expression of a neutrophil adhesion receptor and the subsequent recruitment of neutrophils into the joint.
Corkill
M M
MM
United Medical School, Guy's Hospital, London, UK.
Kirkham
B W
BW
Haskard
D O
DO
Barbatis
C
C
Gibson
T
T
Panayi
G S
GS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D001772:Blood Cell Count / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006046:Gold / Q000494:pharmacology / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D016028:Receptors, Leukocyte-Adhesion / Q000235:genetics / Q000502:physiology*; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D016176:T-Lymphocyte Subsets / Q000473:pathology
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D016028:Receptors, Leukocyte-Adhesion; D000077555:Methylprednisolone Acetate; D006046:Gold; D008775:Methylprednisolone