Effects of ciclosporin and protein synthesis inhibitors on cutaneous inflammation in mouse skin.
Ciclosporin is clinically effective in a variety of inflammatory skin diseases. We have therefore studied the effects of the drug on cutaneous inflammation in mice. Ciclosporin inhibited the inflammatory response to 12-O-tetradecanoylphorbol-13-acetate (TPA) and to the contact sensitising agent oxazolone when applied topically to mouse skin. The drug had no effect on arachidonic acid-induced inflammation. The protein synthesis inhibitor cycloheximide showed a similar profile of activity. Ciclosporin, like actinomycin D but unlike cycloheximide, was only effective in inhibiting the inflammatory response to TPA if given 0.5 h before, but not 2 h, after TPA. These results suggest that the anti-inflammatory activity of ciclosporin in the skin is due to an effect on the production of proinflammatory proteins.
Griffiths
R J
RJ
Department of Pharmacology, Fisons plc Pharmaceutical Division, Loughborough, Leics., UK.
Wood
B E
BE
Li
S
S
Blackham
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D003872:Dermatitis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D010081:Oxazolone / Q000037:antagonists & inhibitors; D009195:Peroxidase / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D003524:Cyclosporins; D011500:Protein Synthesis Inhibitors; D010081:Oxazolone; D003609:Dactinomycin; D016718:Arachidonic Acid; D003513:Cycloheximide; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate