Neuroendocrine Modulation Induced by Selective Blockade of TNF-α in Rheumatoid Arthritis

• Published in: Annals of the New York Academy of Sciences 2006-06, Vol.1069 (1), p.428-437
• Main Authors: DI COMITE, GABRIELE, MARINOSCI, ALESSANDRO, DI MATTEO, PAOLA, MANFREDI, ANGELO, ROVERE-QUERINI, PATRIZIA, BALDISSERA, ELENA, AIELLO, PATRIZIA, CORTI, ANGELO, SABBADINI, MARIA GRAZIA
• Format: Article
• Language: English
• Subjects: Adult; Aged; anti-TNF-α monoclonal antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Chromogranin A; Chromogranins - blood; Humans; Immunotherapy; Infliximab; Middle Aged; Neurosecretory Systems - drug effects; Neurosecretory Systems - physiology; Receptors, Tumor Necrosis Factor - blood; rheumatoid arthritis; tumor necrosis factor receptor-I; tumor necrosis factor receptor-II; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1351.041

:  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.