Resident joint tissues, rather than infiltrating neutrophils and monocytes, are the predominant sources of TNF-alpha in zymosan-induced arthritis.
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.
Pettipher
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Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
Salter
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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
D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan