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Platelet-activating factor (PAF)' is a mediator of inflammation with a wide range of biological activities (see reference 1 for review) . PAF was initially recognized as a product of IgE-sensitized rabbit basophils (2) and was identified with 1-0-alkyl-2-sn-glyceryl-3-phosphorylcholine (3-5). It was subsequently shown that PAF is synthesized after appropriate stimulation by monocytes/macrophages (6-9), polymorphonuclear neutrophils (7, 10, 11), platelets (12) and endothelial cells (13-15) . PAF induces aggregation and degranulation of platelets (2, 16), stimulates contraction of smooth muscle (17), promotes chemotaxis and granule secretion of neutrophils (18-19) and monocytes (20), increases vascular permeability, and alters the vascular tone (21).It was recently suggested that PAF is a mediator of endotoxic shock (22-24) on the basis of the following observations : (a) PAF is produced during endotoxic shock and experimental sepsis by Gram-negative bacteria (23-25) ; (b) infusion of experimental animals with PAF results in hypotension, decrease in cardiac output, and hypovolemic shock (26-28) ; (c) three PAF receptor antagonists (CV3988, kadsurenone, and SRI 63072) inhibit or reverse endotoxin-induced hypotension and, in this way, prolong the survival of rats (22,23,29) .Tumor necrosis factor/cachectin (TNF) is a mediator of endotoxic shock (30). Because TNF administration to experimental animals reproduces several aspects of PAF infusion (30), it seems possible that PAF is synthesized in response to

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Fifteen serum samples and 29 synovial fluids of patients with rheumatoid arthritis (RA) were examined for the presence of tumour necrosis factor (TNF). The assay for TNF was based on the cytotoxic activity of this cytokine for human melanoma cells in tissue culture. High concentrations of TNF were found in serum samples of patients with severe RA, who had increased erythrocyte sedimentation rate and serum a2 macroglobulin, but decreased haemoglobin and serum iron concentrations. Tumour necrosis factor was also found in the synovial fluid of 16 out of 29 patients. High TNF concentrations were found in fluids with >1010 leucocytes/l. Tumour necrosis factor was not detected in the serum of normal subjects or in synovial fluid ofpatients with osteoarthritis. A mediator of inflammation, such as TNF, may contribute to the severity of RA.