title: Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.
abstract: Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.
authors.affiliation: Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Tavares
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliana P
authors.initials: JP
authors.lastname: Vago
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Nathália V
authors.initials: NV
authors.lastname: Batista
authors.affiliation: Department of Clinic, Pathology and Odontological Surgery, Faculty of Odontology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Celso M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Angelica T
authors.initials: AT
authors.lastname: Vieira
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Menezes
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lirlândia P
authors.initials: LP
authors.lastname: Sousa
authors.affiliation: Experimental Rheumatology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Fons A J
authors.initials: FA
authors.lastname: van de Loo
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Flávio A
authors.initials: FA
authors.lastname: Amaral
authors.affiliation: Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Adaliene V M
authors.initials: AV
authors.lastname: Ferreira
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D000068800:Etanercept / Q000494:pharmacology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D007270:Injections, Intra-Articular; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D054392:Adipokines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D000068800:Etanercept; D005947:Glucose; D009419:Nerve Tissue Proteins; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D012710:Serum Albumin, Bovine; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C511776:2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide