Impaired tumour necrosis factor-α (TNF-α) production and abnormal B cell response to TNF-α in patients with systemic lupus erythematosus (SLE)

Abstract

SUMMARYWe examined ihc TNF-x activity in culture supernalants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients wilh SLE stimtilated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan I secreted significantly lower amounts of TNF-a: than did normal monocytes, A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by tnitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNP-5 (rTNF-:() on the B cell function in SLE patients. rTNF-a inhibited the spontaneous Bcell proliferation of SLE. but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibiled by rTNF-a. but that from normal B cells was not. Spontaneous IgG production was unaffecled by rTNF-a. Also. rTNF-x did not affect the viability of B cells. These findings suggest that an Impaired TNF-a production and an abnormal B cell response to TNF-a play a role in the immunological dysfunction in patients with SLE.

Expression of High Mobility Group Box Chromosomal Protein 1 and Its Modulating Effects on Downstream Cytokines in Systemic Lupus Erythematosus

“…B. HMGB1 levels in SLE patients with renal disorder were higher than those in patients without renal disorder and in controls, after production of TNF increases in the whole-blood cell cultures of patients with SLE 36 . However, another study showed a decrease in TNF-α production by cultured SLE monocytes stimulated with LPS 37 . Further, significantly decreased TNF-α production was reported following stimulation of PBMC and peripheral blood leukocytes with phytohemagglutinin 38 .…”

Correlation of antinuclear antibody and anti-double-stranded DNA antibody with clinical response to infliximab in patients with rheumatoid arthritis: a retrospective clinical study

“…First, the direct effect of a decreased serum TNF level caused by a TNF blocker is considered. It has been reported that low levels of TNF-α may promote SLE in predisposed mice and that the treatment of (NZB/NZW) F 1 mice with TNF-α ameliorates nephritis [ 18 ], and low TNF-α expression may be implicated also in human SLE patients [ 19 ]. Thus the blockade of TNF-α itself may favor a lupus-like autoimmunity phenomenon.…”

The Investigation of Cytokines and Oxidative Stress in Patients with Systemic Lupus Erythematosus

“…In its proliferative response to IL-4, B cells can be inhibited by IFN-g, confirming antagonistic actions of these two cytokines. Though IFN-g can induce increased production of antibodies by all or by some B cells, its principal effect is inhibitory and T cell-dependent (30).…”