Comparative effectiveness and molecular pharmacological mechanisms of antiallergic agents on experimental conjunctivitis in mice.
The purpose of this study was to determine the effectiveness of antiallergic agents in the treatment of experimental murine ragweed conjunctivitis. SWR/J mice were divided into eight groups: 1; normal controls (unmanipulated); 2, untreated; 3, lodoxamide; 4, cromolyn; 5, livocarbastine; 6, nedocromil; 7, buffer solution (BS); and 8, tetrandine (TDR). Groups 2-8 were exposed to ragweed pollen through topical application to conjunctival and nasal mucosa, followed by conjunctival challenge with the allergen. Allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) in conjunctiva was analyzed by reverse transcription polymerase chain reaction techniques. Exposed mice developed allergic conjunctivitis clinically and histologically that was modulated by topical lodoxamide, cromolyn, livocarbastine, or nedocromil eye drops or TDR intraperitoneally injected. Histopathologic analysis demonstrated that the drugs and TDR significantly reduced conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1beta and TNF-alpha mRNA gene expression in conjunctiva of treated mice was inhibited compared with untreated and BS-treated controls. No IL-6 mRNA expression was observed even on the conjunctiva of the untreated mice. The antiallergic drugs and TDR exerted a similar action on the murine model of allergic conjunctivitis and demonstrated pharmacologic effectiveness on the conjunctival mRNA expression of cytokines IL-1beta and TNF-alpha.
Hu
S
S
Department of Opthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA.
Merayo-Lloves
J
J
Zhao
T
T
Foster
C S
CS
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D044182:Benzylisoquinolines; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice
D000470:Alkaloids; D018926:Anti-Allergic Agents; D044182:Benzylisoquinolines; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; C009438:tetrandrine