Neuroendocrine modulation induced by selective blockade of TNF-α in rheumatoid arthritis

Tumor necrosis factor-α (TNFα) is a main actor in the pathogenesis of rheumatoid arthritis (RA), interacting with other molecules in complex mechanisms. The neuroendocrine system is known to be involved and Chromogranin A (CHGA) serum levels are elevated in patients with RA. We evaluated the effect of the selective blockade of TNF-α, induced by treatment with anti-TNF-α monoclonal antibodies (mAbs), on the serum levels of CHGA and on its correlation with TNF-α and TNF-α receptors (TNFRs) serum levels. Seven patients with RA have been treated with the anti-TNF-α mAb, infliximab. We measured the serum levels of TNF-α, its receptors (tumor necrosis factor receptor-I [TNFR-I] and tumor necrosis factor receptor-II [TNFR-II]), and CHGA before and during the treatment. We also measured, as a control, the serum levels of CHGA, TNF-α, and soluble TNFRs in 14 patients who were being treated with infliximab, adalimumab, or etanercept and in 20 matching negative controls. The serum levels of TNFR-I and TNFR-II, which are a sensitive marker for the TNF-α pathway, correlated with those of CHGA before treatment (Pearson's coefficient, respectively, 0.59 and 0.53). Treatment with anti-TNF-α mAb provided a significant clinical response in all patients and the correlation between CHGA and TNFR-I and TNFR-II was no more evident during treatment (respectively, -0.09 and -0.07). TNF-α blockade allows a clinical effect in patients with RA and modifies the correlation between CHGA and TNFRs, suggesting that TNF-α and CHGA reciprocally interfere in the pathogenesis of RA, through intermediate adaptors, whose identification warrants further studies.