title: Resident joint tissues, rather than infiltrating neutrophils and monocytes, are the predominant sources of TNF-alpha in zymosan-induced arthritis.
abstract: Intraarticular injection of zymosan (1 mg) into the knee joints of male Wistar rats led to infiltration of neutrophils and monocytes, joint swelling and elevation of tumour necrosis factor (TNF-alpha) in joint lavage fluids. Neutrophil infiltration was maximal at 5 h after induction of arthritis but had declined by 24 h post injection. Monocyte infiltration was maximal around the same time as that of the neutrophil infiltration but was sustained through 24 h. Joint swelling was apparent at 1 h but was not maximal until 6 h after induction of zymosan-induced arthritis. The maximum levels of TNF-alpha (150-200 pg of mouse equivalents per joint) in joint fluid preceded the infiltration of neutrophils and monocytes and was maximal at 1-2 h after injection of zymosan but had declined to below 100 pg per joint at 5 h (the time of maximal leukocyte infiltration) and was below the lower limit of detection at 24 h after induction of arthritis. Depletion of neutrophils and monocytes with a rabbit anti-rat leukocyte antibody reduced leukocyte infiltration and the later phase of joint swelling but did not reduce the levels of TNF-alpha in joint fluid. These data indicate that in zymosan-induced arthritis TNF-alpha is produced from the resident joint tissues such as the synovial lining cells rather than infiltrating neutrophils or monocytes.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Pettipher
authors.forename: E D
authors.initials: ED
authors.lastname: Salter
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007719:Knee Joint / Q000378:metabolism*; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015054:Zymosan
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan