Influence of chylomicron remnants on human monocyte activation in vitro.

BACKGROUND AND AIMS: Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model. METHODS AND RESULTS: Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1. CONCLUSION: Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.

Antibiotic use in otitis media: patient simulations as an aid to audit.

Diagnostic and prescribing practices in otitis media vary, and audit is difficult because doctors may not see comparable cases. Seven general practitioners took part in a pilot study to discover if simulated patients evoked the same diagnostic and treatment responses as reveal patients. Forty-eight patients entered the study over three weeks and provided data for two simulations; one included the doctor's description of the ear and the other a photograph instead. Each doctor was shown the two sets of simulations and asked to state his diagnosis and treatment. The diagnoses each doctor reached agreed significantly with those reached on the simulations of the same patients. The decisions to prescribe antibiotics also showed good agreement.