title: Neuroendocrine modulation induced by selective blockade of TNF-alpha in rheumatoid arthritis.
abstract: Tumor necrosis factor-alpha (TNFalpha) 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-alpha, induced by treatment with anti-TNF-alpha monoclonal antibodies (mAbs), on the serum levels of CHGA and on its correlation with TNF-alpha and TNF-alpha receptors (TNFRs) serum levels. Seven patients with RA have been treated with the anti-TNF-alpha mAb, infliximab. We measured the serum levels of TNF-alpha, 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-alpha, 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-alpha pathway, correlated with those of CHGA before treatment (Pearson's coefficient, respectively, 0.59 and 0.53). Treatment with anti-TNF-alpha 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-alpha blockade allows a clinical effect in patients with RA and modifies the correlation between CHGA and TNFRs, suggesting that TNF-alpha and CHGA reciprocally interfere in the pathogenesis of RA, through intermediate adaptors, whose identification warrants further studies.
authors.affiliation: Clinical Immunology and Rheumatology Unit, CIGTP, H. San Raffaele Scientific Institute-DIBIT and Vita-Salute University, 3A1-Lab 3, via Olgettina 58, 20132 Milan, Italy. dicomite.gabriele@hsr.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: di Comite
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marinosci
authors.forename: Paola
authors.initials: P
authors.lastname: Di Matteo
authors.forename: Angelo
authors.initials: A
authors.lastname: Manfredi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.forename: Elena
authors.initials: E
authors.lastname: Baldissera
authors.forename: Patrizia
authors.initials: P
authors.lastname: Aiello
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sabbadini
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood; D006801:Humans; D007167:Immunotherapy; D000069285:Infliximab; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D053379:Chromogranin A; D002864:Chromogranins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab