RESUMEN
Over the last few years evidence on the major pathophysiological role of cytokines in system lupus erythematosus (SLE) has accumulated. Immunological results were recently confirmed by first clinical trials, which suggest that therapies targeted at the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, as well as the blockade of Interferon, may be highly effective. Controlled clinical trials will have to prove this concept over the next few years.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Interleucina-6/antagonistas & inhibidores , Interleucina-6/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , HumanosRESUMEN
In systemic lupus erythematosus (SLE) serum TNF is increased and correlates with its soluble receptors and with disease activity. We therefore investigated (i) whether the TNF in SLE serum is bioactive, (ii) whether SLE cells react to TNF and (iii) whether there are associations with cell death, which is regarded as pathogenic in SLE. Sera from active SLE patients induced an increase in fibroblast CD54, which was abolished by blocking antibodies against TNF, suggesting TNF bioactivity. SLE lymphocytes had a similar surface expression of TNF-RI as healthy lymphocytes, their expression of TNF-RII was slightly increased. Recombinant TNF induced cell death in PBMC of SLE patients, suggesting functional receptors. Serum levels of sTNF-RII (as a surrogate marker for TNF activity) correlated with sTNF-RI and disease activity, as expected, and also correlated with the percentage of dying lymphocytes and with lymphocytic CD95. SLE sera contain increased amounts of biologically active TNF. Peripheral blood lymphocytes of SLE patients express functional TNF receptors. Finally, associations with cell death and CD95 receptors suggest that TNF may be pathogenic in SLE.
