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Lupus, Vol. 11, No. 2, 102-108 (2002)
DOI: 10.1191/0961203302lu160oa

Increased bioactive TNF in human systemic lupus erythematosus: associations with cell death

M Aringer

Department of Rheumatology, Internal Medicine II, University of Vienna, Austria; Department of Rheumatology, Internal Medicine III, University of Vienna, AKH, Waehringer Guertel 18-20, A-1090 Wien, Austria martin.aringer{at}akh-wien.ac.at

E Feierl

G Steiner

G H Stummvoll

Department of Rheumatology, Internal Medicine II, University of Vienna, Austria

E Höfler

Department of Internal Medicine II, Lainz Hospital, Vienna, Austria

C W Steiner

I Radda

Department of Rheumatology, Internal Medicine II, University of Vienna, Austria

J S Smolen

Department of Rheumatology, Internal Medicine II, University of Vienna, Austria; Department of Internal Medicine II, Lainz Hospital, Vienna, Austria

W B Graninger

Department of Rheumatology, Internal Medicine II, University of Vienna, Austria

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-R I as healthy lymphocytes, their expression of TNF-R II 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.

Key Words: SLE • TNF • TNF-receptor • apoptosis • CD95


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