Increased neutralization capacity of TNF-α in sera of relapsing remitting multiple sclerosis patients is not related to soluble TNF-α receptors or anti-TNF-α autoantibody levels

The increased TNF-α levels in active lesions and CSF of multiple sclerosis (MS) patients and the beneficial effect of TNF-α blockade in animal models of MS led to the therapeutic usage of TNF-α antagonists. However, systemic TNF-α blockade exacerbated MS activity and was associated with new-onset MS when implemented for treating other autoimmune disorders. We employed a TNF-α neutralization bioassay and demonstrated that the capacity of sera from untreated and IFN-β-treated relapsing remitting MS patients to neutralize TNF-α is significantly higher than that of matched healthy controls. This finding was not related to sTNFRI, sTNFRII, or anti-TNF-α Abs levels.