Pulse methylprednisolone in rheumatoid arthritis: effects on peripheral blood and synovial fluid neutrophil surface phenotype.
OBJECTIVE
To determine the effects of a 1000 mg intravenous pulse of methylprednisolone (MP) on the expression of cell adhesion molecules on peripheral blood and synovial fluid (SF) neutrophils in rheumatoid arthritis.


METHODS
Fluorescent flow cytometric analysis was performed on peripheral blood neutrophils (n = 13 patients) and knee joint SF neutrophils (n = 7 patients) prior and at 4 and 24 h after MP. Clinical and laboratory assessments of disease activity were performed.


RESULTS
There was marked improvement in all clinical stores at 24 h including a decrease in pain score (p < 0.0005), stiffness (p < 0.00005), joint tenderness score and modified Health Assessment Questionnaire (HAQ) (p < 0.005), and an increase in well being (p < 0.001). At 24 h there was a significant decrease in SF neutrophil counts to mean (SEM) of 31.5% (15%) of baseline and an increase in peripheral blood neutrophils to a mean (SEM) of 199% (25%) of baseline. Furthermore, a significant decrease was observed in the expression of both structural and functional epitopes of CD11b (p < 0.05) and CD18 (p < 0.05) on SF neutrophils at both 4 and 24 h post-MP. There was also an increase in the expression of L-selectin (CD62L), which approached significance (p = 0.01), but no significant effect on CD11a, CD44 and sialyl Lewisx (CD15s). Peripheral blood neutrophils showed decreased expression of CD11b (p = 0.1), CD18 (p = 0.07), and L-selectin (p = 0.09), which approached statistical significance without any associated effects on CD11a, CD15s, or CD44.


CONCLUSIONS
MP is associated with a marked decrease in CD11b and CD18 expression on SF neutrophils and, to a lesser extent, peripheral blood neutrophils. This may be due to decreased neutrophil activation as these cells traffic from the vasculature through the synovial membrane or to decreased activation in the synovial space.
Youssef
P
P
Rheumatology Unit, Repatriation General Hospital, Daw Park, Adelaide, South Australia.
Roberts-Thomson
P
P
Ahern
M
M
Smith
M
M
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016023:Integrins / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype; D019087:Selectins / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016023:Integrins; D019087:Selectins; D008775:Methylprednisolone