Interleukin-18 reduces expression of cardiac tumor necrosis factor-alpha and atrial natriuretic peptide in a murine model of viral myocarditis.
Heart failure is generally believed to begin with myocyte damage caused by a variety of insults, including ischemia, toxin or myocardial infection. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been hypothesized to play a pathogenetic role in the transition from compensated to decompensated heart failure. Interleukin-18 (IL-18), a recently cloned cytokine synthesized by Kupffer cells, activates macrophages. We examined the therapeutic effect of IL-18 on the modulation of TNF-alpha gene expression in failing heart in a murine model of heart failure caused by viral myocarditis. The heart weight (HW)/ body weight (BW) ratio in IL-18 treated mice 7 days after viral inoculation was significantly lower (P<0.01) than in the untreated controls. Myocardial necrosis and inflammatory cell infiltration were significantly lower in IL-18 treated mice than untreated mice 5 and 7 days after inoculation. The expression of TNF-alpha mRNA in the myocardium was significantly lower on days 5 and 7 in IL-18 treated mice than in infected untreated mice. We conclude that concurrent systemic administration of IL-18 is beneficial in mice with myocarditis, and may be mediated through reduced expression of TNF-alpha in the heart.
Yoshida
Akihiro
A
Department of Laboratory Medicine Gunma University School of Medicine, Maebashi, Japan.
Kand
Tsugiyasu
T
Tanaka
Toru
T
Yokoyama
Tomoyuki
T
Kurimoto
Masashi
M
Tamura
Junichi
J
Kobayashi
Isao
I
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020382:Interleukin-18 / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D020382:Interleukin-18; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D009320:Atrial Natriuretic Factor