title: Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis.
abstract: BACKGROUND
  Nanocrystalline silver has both antimicrobial and anti-inflammatory properties. However, the exact mechanisms underlying these activities are not known.
  
  
  OBJECTIVE
  The objectives of this study were to assess the anti-inflammatory effects of nanocrystalline silver using a murine model of allergic contact dermatitis, compare the effects with those of tacrolimus and a high potency steroid, and to relate the effects to modulation of pro-inflammatory cytokines and apoptosis of inflammatory cells.
  
  
  METHODS
  Dermatitis was induced on the ears of BALB/c mice using dinitrofluorobenzene. Topical treatment, including vehicles, 1% nanocrystalline silver cream, tacrolimus ointment and a high potency steroid, was applied once a day for 4 days. Ear swelling was measured and the erythema was evaluated daily. After 4 days of treatment the mice were killed and samples from the ears were collected for histological and immunohistochemical examination, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) staining and extraction of total RNA for reverse transcriptase polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Significant reductions of ear swelling, erythema and histopathological inflammation in mice ears were observed after 4 days of treatment with 1% nanocrystalline silver cream, tacrolimus ointment or a high potency steroid with no significant difference among them. Both RT-PCR and immunohistochemical staining of sections from ear biopsies demonstrated that nanocrystalline silver, tacrolimus and steroid significantly suppressed the expression of tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. TUNEL staining demonstrated a significant increase in the numbers of apoptotic cells in material from the group treated with nanocrystalline silver when compared with that from groups treated with vehicle, tacrolimus or steroid.
  
  
  CONCLUSIONS
  This study demonstrates that nanocrystalline silver inhibits allergic contact dermatitis in mice, similar to steroid and tacrolimus. Nanocrystalline silver suppresses the expression of TNF-alpha and IL-12 and induces apoptosis of inflammatory cells; mechanisms by which nanocrystalline silver may exert its anti-inflammatory effects.
authors.affiliation: NUCRYST Pharmaceuticals Inc., 50 Audubon Road, Wakefield, MA 01880, USA. kbhol@nucryst.com
authors.forename: K C
authors.initials: KC
authors.lastname: Bhol
authors.forename: P J
authors.initials: PJ
authors.lastname: Schechter
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis; D003460:Crystallization; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000276:immunology; D004139:Dinitrofluorobenzene; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D049329:Nanostructures; D009824:Ointments; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012834:Silver / Q000627:therapeutic use*; D013194:Staining and Labeling; D016559:Tacrolimus / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009824:Ointments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D012834:Silver; D004139:Dinitrofluorobenzene; D016559:Tacrolimus