Inhibition of PAF-, LPS-, and cytokine-induced granulocyte accumulation in guinea pig lung by dexamethasone: evidence that inhibition of IL-5 release is responsible for the selective inhibition of eosinophilia by glucocorticoids in guinea-pigs.
The potency of dexamethasone has been determined as an inhibitor of intratracheally administered platelet activating factor- (PAF), or interleukin (IL)-5-induced eosinophilia, and of lipopolysaccharide-(LPS), tumour necrosis factor alpha-(TNF alpha) or cytokine-induced neutrophil chemoattractant- (CINC) induced neutrophilia in guinea-pig lungs. Dexamethasone was a potent inhibitor of PAF- induced eosinophil accumulation, but higher doses of dexamethasone were required to inhibit IL-5-induced eosinophilia. LPS-induced neutrophilia was less sensitive to the inhibitory effects of dexamethasone, than PAF-induced eosinophilia. Both LPS- and TNF alpha-induced neutrophilia were inhibited by the same doses of dexamethasone. In contrast, higher doses of dexamethasone were required to inhibit CINC-induced neutrophilia. Since data in the literature show that PAF-induced eosinophilia in guinea-pig lungs is dependent on the generation of IL-5, it is concluded that inhibition of this response, by dexamethasone, is due to inhibition of release of IL-5. Similarly, although data in the literature show that LPS-induced neutrophilia is dependent on the generation of TNF alpha, it is concluded that inhibition of this response, by glucocorticoids, is due to an action on an event which occurs after the release of TNF alpha, possibly through inhibition of chemokine release.
Whelan
C J
CJ
Division of Biosciences, School of Natural Sciences, University of Hertfordshire, Hatfield, Herts, UK.
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000008:administration & dosage / Q000633:toxicity; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000139:chemically induced / Q000188:drug therapy*; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D006133:Growth Substances / Q000008:administration & dosage / Q000633:toxicity; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D015848:Interleukin-5 / Q000008:administration & dosage / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000633:toxicity; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D002630:Chemotactic Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D015848:Interleukin-5; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone