Involvement of platelet-activating factor and tumour necrosis factor in the pathogenesis of joint inflammation in rabbits.
We have studied the participation of platelet-activating factor (PAF) in antigen-induced arthritis in rabbits, as well as the possible co-operation between PAF and tumour necrosis factor (TNF) in their ability to induce joint inflammation when injected into the knees of healthy rabbits. The administration of two structurally different PAF receptor antagonists, BN52021 and Alprazolam, from 4 h before the intra-articular injection of ovalbumin in preimmunized rabbits, induced an important reduction in the synovial fluid volume, in the amount of cells infiltrating the articular cavity and the synovial membrane, as well as in the prostaglandin E2 (PGE2) concentration. Furthermore, proteoglycans of the articular cartilage, which were found diminished in animals with non-treated arthritis, were well preserved in rabbits treated with PAF antagonists. All the synovial fluids from joints with arthritis had detectable amounts of PAF. The injection of either TNF or PAF into the joints of normal rabbits induced a mild inflammation. When TNF was administered 1 h before PAF, a synergistic response was noted in the synovial fluid volume, in the accumulation of leucocytes, and in the amount of PGE2. The administration of BN50726, a hetrazepine with a potent PAF-receptor antagonist effect, induced a diminution in those parameters. Our results suggest that PAF may be an early and important mediator of joint damage, and that TNF can amplify the inflammatory response induced by PAF. PAF receptor antagonists could play some role in the treatment of inflammatory joint diseases.
Zarco
P
P
Fundación Jiménez Díaz, Universidad Autónoma, Spain.
Maestre
C
C
Herrero-Beaumont
G
G
González
E
E
Garcia-Hoyo
R
R
Navarro
F J
FJ
Braquet
P
P
Egido
J
J
D000818:Animals; D001168:Arthritis / Q000139:chemically induced; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D001381:Azepines / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology* / Q000633:toxicity
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C061327:BN 50726; D015232:Dinoprostone