title: Neutrophils of rheumatoid arthritis patients on anti-TNF-α therapy and in disease remission present reduced adhesive functions in association with decreased circulating neutrophil-attractant chemokine levels.
abstract: Neutrophils participate in the initiation and progression of rheumatoid arthritis (RA) although the exact mechanisms responsible for neutrophil accumulation in rheumatoid joints are not understood. This study compared the adhesive and chemotactic functions of neutrophils from RA patients in activity (DAS28 > 3.2) and not in activity (DAS28 < 2.6) and observed the effects of different treatment approaches on these functions. Neutrophils were isolated from healthy controls (CON), and patients with active or inactive RA in use of therapy not specific for RA (NSAIDs), in use of DMARDs and in use of anti-TNF-α therapy. Adhesive and chemotactic properties were evaluated using in vitro assays; adhesion molecule expression was assessed by flow cytometry and real-time PCR and circulating chemokines were determined by ELISA. No significant alterations in the adhesive and chemotactic properties of neutrophils from active RA were observed when compared to CON neutrophils, independently of treatment regimen. In contrast, neutrophils from RA patients in disease remission presented reduced adhesive properties and a lower spontaneous chemotactic capacity, in association with decreased adhesion molecule expression, although profiles of alterations differed for those patients on DMARDs and those on anti-TNF-α therapy. Circulating levels of the major neutrophilic chemokines, IL-8 and epithelial neutrophil activating peptide-78, were also significantly decreased in those patients demonstrating a clinical response. Remission of RA appears to be associated with ameliorations in aspects important for neutrophil adhesion and chemotaxis; whether these alterations contribute to decrease neutrophil migration to the synovial fluid, with consequent improvements in the clinical manifestations of RA, remains to be determined.
authors.affiliation: Hematology and Hemotherapy Center, INCTS, School of Medicine, University of Campinas-UNICAMP, Campinas, Sao Paulo, Brazil.
authors.forename: V M
authors.initials: VM
authors.lastname: Dominical
authors.forename: M B
authors.initials: MB
authors.lastname: Bértolo
authors.forename: C B
authors.initials: CB
authors.lastname: Almeida
authors.forename: V T
authors.initials: VT
authors.lastname: Garrido
authors.forename: L I
authors.initials: LI
authors.lastname: Miguel
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
authors.forename: N
authors.initials: N
authors.lastname: Conran
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000097:blood*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000069285:Infliximab; D016209:Interleukin-8 / Q000097:blood / Q000494:pharmacology; D019041:L-Selectin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D000069285:Infliximab