Therapeutic blockade of TNF in patients with SLE-promising or crazy?

Autoimmun Rev. 2012 Mar;11(5):321-5. doi: 10.1016/j.autrev.2011.05.001. Epub 2011 May 18.


TNF is an important mediator of inflammation, but is also involved in the control of autoimmunity. The latter has been demonstrated in a murine model of SLE (NZB/W) and by the occurrence of autoantibodies to nuclear antigens as well as occasional, transient lupus-like syndromes in patients under TNF blockade. In contrast, data on increased TNF levels in serum, kidney and skin samples of SLE patients as well as results in other mouse models of the disease point to an inflammatory role of TNF in SLE organ disease. Despite all due caution, given these two sides of the cytokine, TNF blockade has by now been employed for several years in single cases and open label studies; data on more than fifty patients have meanwhile been published, for the vast majority of which infliximab was employed. These clinical data have to be very cautiously interpreted, as always with data on single cases or open label trials. However, some consistent pieces of information emerge and may inform controlled clinical trials: (i) While antibodies to double-stranded DNA commonly showed transient increases, lupus flares have not been seen so far and thus apparently are at least not the rule; (ii) in contrast, increases in anti-phospholipid antibodies may be associated with vascular adverse events; (iii) bacterial infections, pneumonia and urinary tract infections in particular, have been observed; (iv) short term induction therapy appears relatively safe, while long-term TNF blockade may confer significant risks in SLE; (v) TNF blocker induction therapy may lead to long-term remission in patients with lupus nephritis, hemophagocytic syndrome, and interstitial lung disease; (vi) patients with lupus arthritis often respond to TNF-blockade but symptoms recur after cessation of therapy, necessitating longer term therapy, which is more risky than short term treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmunity / immunology
  • Disease Models, Animal
  • Humans
  • Infections / complications
  • Inflammation / immunology
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lymphoma / complications
  • Mice
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology


  • Autoantibodies
  • Tumor Necrosis Factor-alpha