[Modulators of leukocytic functions].
Polymorphonuclear neutrophils (PMN) and monocytes play a role in vascular diseases. Animal experimental models, using deleukocytation or injection of anti-CD11b-anti-CD18 monoclonal antibodies (inhibition of leukocytic adhesion and of interaction with the endothelial cell) have confirmed this role in the ischemia-reperfusion syndrome and in myocardial infarction. In man, increased production of oxygen radicals, PMN release of elastase, increased monocyte formation of tissue factor (TF) and integrins have been noted in coronary artery disease, in chronic arteriopathy of the lower limbs and in association with vascular risk factors such as diabetes. Pharmacological alteration of leukocyte hyperactivity therefore seems to be justified. Pentoxifylline, used with good effect in arteriopathy of the lower limbs, affects numerous leukocytic functions: diminution in adherence and in PMN production of free radicals, diminution in the formation of TF and cytokines (TNF). Gingkolides reduce leukocytic interactions and platelet activation through an anti-PAF (Platelet Activation Factor) action. Aspirin may interfere with free radicals and inhibit TF formation. alpha-tocopherol blocks the activation, by free radicals, of the transcription factor NF k B. By altering the TNF and IL-1 cytokines, leukocytic activation can be controlled. Other cytokines (IL-4, IL-10) have an immunosuppressive action and reduce the formation of TF. The pharmacological targets are therefore multiple. Their use in vascular diseases is only at a very preliminary stage.
Nguyen
P
P
Laboratoire central d'Hématologie, CHU Robert Debré, Reims.
Broussas
M
M
Hézard
N
N
Cornillet
P
P
Potron
G
G
D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D005609:Free Radicals; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D014652:Vascular Diseases / Q000188:drug therapy / Q000209:etiology
D005609:Free Radicals; D010972:Platelet Activating Factor; D000242:Cyclic AMP
Les modificateurs des fonctions leucocytaires.