Effects of dexamethasone and cyclosporin A on the accumulation of eosinophils in acute cutaneous inflammation in the guinea-pig.
1. Eosinophils are thought to play an important role in the pathophysiology of allergic diseases and pharmacological suppression of their recruitment is considered to be of therapeutic benefit. In the present study we have assessed and compared the effects of treatment with dexamethasone and cyclosporin A on the accumulation of 111In-labelled eosinophils and local oedema formation in sites of acute inflammation in guinea-pig skin. 2. When injected locally 150 min prior to i.d. administration of antigen in a passive cutaneous anaphylactic (PCA) reaction, dexamethasone (10(-9) to 3 x 10(-7) mol per site) dose-dependently inhibited oedema formation by up to 50%. Similarly, oedema formation induced by PAF and lipopolysaccharide (LPS), but not by zymosan-activated plasma (ZAP), was significantly inhibited by dexamethasone. In contrast, 111In-eosinophil accumulation measured in response to i.d. injection of PAF, LPS and ZAP or in the PCA reaction was not altered. 3. Systemic treatment with dexamethasone (4 mg kg-1, i.v., 150 min pretreatment period) inhibited both oedema formation and 111In-eosinophil accumulation induced by PAF, ZAP, LPS and in the PCA reaction. 4. The effects of i.d. injection of cyclohexamide (2 x 10(-7) mol per site) on 111In-eosinophil accumulation and oedema formation induced by PAF, ZAP or in a PCA reaction were evaluated in order to assess the dependency of these responses on protein synthesis. Cycloheximide had no effect on the responses measured. In contrast, 111In-eosinophil accumulation, but oedema formation, induced by LPS was inhibited by 30%. 5. Acute (10 mg kg-1, i.v., 15 min pretreatment) or prolonged (10 mg kg-1, s.c. daily for 3 days) systemic treatment with cyclosporin A had no effect on 111In-eosinophil accumulation or oedema formation induced by PAF, ZAP, LPS or in the PCA reaction. 6. In conclusion, we demonstrate preferential inhibitory effects of dexamethasone on 111In-eosinophil accumulation according to its site of administration. In addition we show that dexamethasone inhibits protein synthesis-independent acute inflammation in guinea-pig skin. Finally, our results do not support the concept that eosinophils are an important cellular site of action for the inhibitory effects of cyclosporin A in a guinea-pig model of allergic inflammation.
Teixeira
M M
MM
National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London.
Williams
T J
TJ
Hellewell
P G
PG
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000473:pathology / Q000517:prevention & control*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine; D003513:Cycloheximide