Inhibition of leukocyte chemotaxis by immunosuppressive agents. Specific inhibition of lymphocyte chemotaxis by cyclosporine.
Since chemotaxis is an important mechanism by which leukocytes are recruited to allografts during rejection, the effect of immunosuppressant agents on in vitro chemotactic responses of neutrophils, monocytes, and lymphocytes was studied. Cyclosporine caused profound inhibition of lymphocyte chemotaxis to three different chemotactic factors at pharmacologic levels but had no effect on neutrophil or monocyte chemotaxis. Methylprednisolone and azathioprine both inhibited chemotactic responses of neutrophils and monocytes as well as lymphocytes. These data suggest that immunosuppressant agents are potent inhibitors of leukocyte chemotaxis and that drugs differ as to which leukocyte cell type they inhibit. The selective action of cyclosporine might explain why this drug is ineffective in reversing established rejection episodes in which monocytes and neutrophils are also involved. Inhibition of leukocyte chemotaxis may be an important mode of action of immunosuppressant drugs, and drug regimes might be adjusted to cause selective inhibition of particular cell types.
Adams
D H
DH
Liver Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, England.
Wang
L F
LF
Neuberger
J M
JM
Elias
E
E
D001379:Azathioprine / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects*; D008775:Methylprednisolone / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects
D003524:Cyclosporins; D001379:Azathioprine; D008775:Methylprednisolone