Platelet activating factor (PAF) has many proinflammatory properties. It is a polymorphonuclear leukocyte
chemotactic factor, it aggregates platelets, increases vascular permeability, and is generated by inflammatory cells. To determine the possible in vivo role of PAF in
inflammation, we examined the effects of the PAF antagonist and structural analogue,
CV3988 on acute inflammatory responses in the skin of rabbits. Initial experiments indicated that
CV3988 (10 mg/kg) was a specific inhibitor of PAF responses in vivo since it abolished
neutropenia and
thrombocytopenia induced by intravenous (iv) PAF infusion without effecting the response to
f-met-leu-phe. In dermal
inflammation, 125I-albumin, 111In-labeled platelets, 51Cr-labeled leukocytes, and 86RbCl were used to simultaneously quantitate
protein exudation, platelet deposition, leukocyte accumulation, and blood flow in the lesions.
CV3988 inhibited inflammatory responses to
intradermal injection of PAF by 65 to 85% but it did not inhibit
thrombin-induced platelet deposition or
bradykinin and
histamine-induced
protein exudation.
CV3988 treatment inhibited by 60 to 80% (p less than 0.01) the platelet deposition occurring at the peak of the reaction (1 1/2 hours) induced by the
intradermal injection of
zymosan,
zymosan activated plasma,
endotoxin, and the reversed passive
Arthus reaction.
Protein exudation was inhibited by 67 to 85% (p less than 0.1) and leukocyte accumulation was inhibited by 24 to 35% (p less than 0.05), but only in the
zymosan and reversed passive Arthus reactions, respectively. Inflammatory
hyperemia (increases blood flow) was not affected by
CV3988 treatment. We conclude that in certain inflammatory reactions, PAF may mediate platelet deposition and
protein exudation. The marginal effect of
CV3988 on leukocyte accumulation suggests that the leukotactic activity of PAF is relatively less important in vivo.