title: Control of middle ear inflammatory and ion homeostasis genes by transtympanic glucocorticoid and mineralocorticoid treatments.
abstract: OBJECTIVE
  Transtympanic steroid treatment will induce changes in ion homeostasis and inflammatory gene expression to decrease middle ear inflammation due to bacterial inoculation.
  
  
  BACKGROUND
  Otitis media is common, but treatment options are limited to systemic antibiotic therapy or surgical intervention. Systemic glucocorticoid treatment of mice decreases inflammation and improves fluid clearance. However, transtympanic delivery of glucocorticoids or mineralocorticoid has not been explored to determine if direct steroid application is beneficial.
  
  
  METHODS
  Balb/c mice received transtympanic inoculation of heat-killed Haemophilus influenzae (H flu), followed by transtympanic treatment with either prednisolone or aldosterone. Mice given PBS instead of steroid and untreated mice were used as controls. Four hours after steroid treatment, middle ears were harvested for mRNA extraction and 24 hours after inoculation middle ears were harvested and examined for measures of inflammation.
  
  
  RESULTS
  H flu inoculation caused the increased expression of nearly all inflammatory cytokine genes and induced changes in expression of several genes related to cellular junctions and transport channels. Both steroids generally reversed the expression of inflammatory genes and caused ion and water regulatory genes to return to normal or near normal levels. Histologic evaluation of middle ears showed improved fluid and inflammatory cell clearance.
  
  
  CONCLUSIONS
  Improvement in middle ear inflammation was noted with both the glucocorticoid prednisolone and the mineralocorticoid aldosterone. This was due to reversal of inflammation-induced changes in middle ear cytokine genes, as well as those involved in ion and water homeostasis. Because glucocorticoids bind to the mineralocorticoid receptor, but not the reverse, it is concluded that much of the reduction of fluid and other inflammation measures was due to these steroids impact on ion and water transport channels. Further research is necessary to determine if this alternative mineralocorticoid treatment for otitis media will be clinically effective with fewer side effects than glucocorticoids.
authors: Oregon Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239-3098, United States of America.
authors: Jessyka G
authors: JG
authors: Lighthall
authors: Oregon Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239-3098, United States of America.
authors: J Beth
authors: JB
authors: Kempton
authors: Oregon Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239-3098, United States of America.
authors: Frances
authors: F
authors: Hausman
authors: Oregon Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239-3098, United States of America.
authors: Carol J
authors: CJ
authors: MacArthur
authors: Oregon Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239-3098, United States of America.
authors: Dennis R
authors: DR
authors: Trune
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D007477:Ions / Q000378:metabolism*; D051379:Mice; D008901:Mineralocorticoids / Q000494:pharmacology*; D010033:Otitis Media / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D007477:Ions; D008901:Mineralocorticoids