Effects of anti-inflammatory agents on lymphocyte migration stimulated by the interferons, tumor necrosis factor and cutaneous inflammation.
Our goal was to examine the effect of anti-inflammatory agents on the migration of lymphocytes to cutaneous inflammatory sites and in response to cytokines. The accumulation of i.v. injected 111In-labelled peritoneal exudate lymphocytes in skin sites of rats injected with KLH to induce DTH reactions, LPS, poly I:C and the cytokines, IFN-gamma, IFN-alpha/beta and tumor necrosis factor was determined. Systemic dexamethasone (DEX) treatment strongly inhibited the migration of lymphocytes in response to all of the stimuli, however, the effective dose of DEX varied widely with the different recruiting agents. The lowest ED50 was observed with LPS, while IFN-alpha/beta was the least inhibited. DEX treatment increased lymphocyte accumulation in the bone marrow and spleen. Pretreatment of lymphocytes with DEX had no effect on their migration, while local i.d. hydrocortisone inhibited migration into the skin. Cyclosporin A treatment had no effect on lymphocyte recruitment in response to any of the cytokines or LPS but significantly inhibited migration to DTH reactions and poly I:C. Treatment of rats with indomethacin, ASA and BW755C produced only a marginal inhibition of lymphocyte migration in response to some of the stimuli tested. DEX is a potent inhibitor of lymphocyte migration to inflammation. In addition to suppressing cytokine production, it can suppress migration to cytokines, probably through inhibiting the effects of these agents on the vascular endothelium. Cyclosporin A decreases lymphocyte accumulation only through its ability to suppress lymphokine production, while inhibitors of arachidonate metabolism have little direct effect on lymphocyte migration.
Issekutz
T B
TB
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D003872:Dermatitis / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D003524:Cyclosporins; D011448:Prostaglandin Antagonists; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007372:Interferons