title: LCB 2183 inhibits the inflammation associated with oxazolone-induced contact sensitivity.
abstract: LCB 2183, an anti-allergic and potential anti-asthma compound, has been investigated for its ability to inhibit contact sensitivity in the mouse. The delayed response to epicutaneous hapten challenge in this model is a classical T-cell-mediated inflammatory reaction which is dependent on an early initiation phase. Both the early and late components of oxazolone-induced contact sensitivity were inhibited by oral administration of LCB 2183 in a dose-dependent manner. The drug appears to act on the efferent limb of the response since administration before hapten challenge was effective, while administration before the initial sensitization was not. LCB 2183 acts early in the cascade of events leading to inflammation, since the initiation phase of the response was inhibited; nonetheless, an effect of the drug on the late acting inflammatory cells cannot be ruled out. In comparison with oral prednisolone, which was also able to inhibit both the early and late components of the response, LCB 2183 was less active. Sodium cromoglycate and nedocromil sodium, which are poorly absorbed from the gastrointestinal tract, were tested by intraperitoneal administration. Neither of these agents significantly altered the delayed response and only nedocromil sodium had a limited inhibitory effect on the early initiation phase. Thus, in this model, LCB 2183 demonstrated more anti-inflammatory potential and resembled prednisolone more closely than either nedocromil sodium or sodium cromoglycate. The possible relevance of these effects in relation to the inflammation which characterizes human asthma is considered.
authors.affiliation: Lipha SA, Vevey, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Murray
authors.forename: N
authors.initials: N
authors.lastname: Zoerkler
authors.forename: T
authors.initials: T
authors.lastname: Brown
authors.forename: Y
authors.initials: Y
authors.lastname: Bonhomme
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004205:Cromolyn Sodium / Q000494:pharmacology / Q000627:therapeutic use; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000209:etiology; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000188:drug therapy* / Q000209:etiology; D004353:Drug Evaluation, Preclinical; D004423:Ear; D004487:Edema / Q000517:prevention & control; D005260:Female; D051379:Mice; D008808:Mice, Inbred CBA; D017835:Nedocromil / Q000494:pharmacology / Q000627:therapeutic use; D010081:Oxazolone / Q000633:toxicity*; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D011622:Pterins; D016176:T-Lymphocyte Subsets / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011622:Pterins; D017835:Nedocromil; D010081:Oxazolone; C090847:LCB 2183; D011239:Prednisolone; D004205:Cromolyn Sodium