Effect of 10 pharmacologic probes on mRNA levels of inducible nitric oxide synthetase and selected inflammatory cytokines in a rat model of acute otitis media.
Ten drugs were screened for their ability to decrease inflammatory mediator (IL-6, inducible nitric oxide synthetase [iNOS], IL-1beta and monocyte chemotactic protein [MCP-1]) expression in a rat model of acute otitis media caused by Streptococcus pneumoniae. Six adult rats were randomly assigned to each of 12 groups corresponding to uninfected controls and treatments with saline, aminoguanidine, anisomycin, dexamethasone, ketorolac, L-N(G)-nitroarginine methylester, methylprednisolone, mycophenolic acid, pentoxiphylline, tacrolimus or WEB2086. Forty-eight h after the start of treatment, the ears of the animals in the 11 treatment groups were challenged with S. pneumoniae. Forty-eight h later, all animals were killed and middle ear mucosa was harvested and assayed for RNA message. Messages for IL-6, iNOS and MCP-1 were significantly increased as a result of infection. Most treatments decreased MCP-1 and four decreased IL-6 and iNOS. Tacrolimus and dexamethasone decreased IL-6, iNOS and MCP-1. These results show that pharmacological agents can modify the expression of inflammatory mediators in this model and may have clinically relevant effects.
Hebda
Patricia A
PA
Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213-2583, USA. hebda@pitt.edu
Burckar
Gilbert J
GJ
Alper
Cuneyt M
CM
Swarts
J Douglas
JD
Moody-Antonio
Stephanie
S
Zeevi
Adriana
A
Doyle
William J
WJ
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000188:drug therapy*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat