Induction of TNF-alpha and proinflammatory secretory phospholipase A2 by intravenous administration of CAMPATH-1H in patients with rheumatoid arthritis.
OBJECTIVE
To test the effect of infusions of CAMPATH-1H on levels of proinflammatory secretory phospholipase A2 (sPLA2) and tumor necrosis factor alpha (TNF-alpha) in patients with rheumatoid arthritis (RA).


METHODS
Two patients with RA were infused with CAMPATH-1H; extracellular nonpancreatic sPLA2 activity was tested using radiolabelled E. coli membrane phospholipid, and circulating TNF-alpha levels were tested by ultrasensitive immunoassay.


RESULTS
Circulating TNF-alpha began to rise within the first 2 h after infusion, reaching > 1000-fold values compared to preinfusion levels. Circulating sPLA2 activity began to rise a few hours after the start of infusion and reached extremely high values in 12 h, concomitant with fever and hypotension. The activity of sPLA2 decreased to pretreatment values in 3-18 days after infusion.


CONCLUSIONS
The mechanism leading to the increase of TNF-alpha and hyperphospholipasemia A2 has not been elucidated. It is possible that CAMPATH-1H activates cells that synthesize and release TNF-alpha and sPLA2, and/or that it induces interleukin 2 release, which in turn activates TNF-alpha, with subsequent release of sPLA2.
Pruzanski
W
W
Inflammation Research Group and Rheumatic Disease Unit, Wellesley Hospital, University of Toronto, Canada.
Urowitz
M B
MB
Grouix
B
B
Vadas
P
P
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D018836:Inflammation Mediators / Q000097:blood*; D007275:Injections, Intravenous; D010741:Phospholipases A / Q000097:blood* / Q000378:metabolism; D054467:Phospholipases A2; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D000074323:Alemtuzumab; D010741:Phospholipases A; D054467:Phospholipases A2