Effect of interleukin-15 on the course of myocarditis in Coxsackievirus B3-infected BALB/c mice.
OBJECTIVE
Cytokines have an important role in both the initiation and perpetuation of viral myocarditis. Because a causative therapy of myocarditis is not yet well established and immunomodulation is a promising approach, the influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined.


METHODS
Hearts from CVB3-infected (n=14), sham-infected (n=14) and CVB3-infected BALB/c mice treated with IL-15 (n=6) or a competitive IL-15 fusion protein (n=6) were analyzed for hemodynamic function, cellular infiltrates and myocardial collagen content.


RESULTS
Induction of myocarditis was associated with significant loss of body and heart weight, decreased left ventricular function, and increased collagen content and cellular infiltrates in the myocardium. Treatment of infected animals with IL-15 resulted in normalization of body and heart weight, and significantly improved systolic and diastolic left ventricular function, comparable with that of uninfected animals. This was paralleled by a significant reduction of myocardial collagen content to levels observed in animals without disease and by markedly reduced cellular infiltration of lymphocytes and macrophages in the myocardium. Inhibition of intrinsic IL-15 with IL-15 fusion protein tended to aggravate the disease.


CONCLUSIONS
Treatment with IL-15 has a positive effect on CVB3- induced murine myocarditis and seems to be a promising approach to modifying clinical course, hemodynamics and histopathology of virus-induced myocarditis. Further studies are needed to identify the underlying mechanisms.
Bigalke
Boris
B
Medizinische Klinik III, Klinik für Kardiologie und Kreislauferkrankungen, Eberhard Kearls Universität Tübingen, D-72076 Tübingen, Germany.
Schwimmbeck
Peter L
PL
Haas
Christian S
CS
Lindemann
Stephan
S
D000818:Animals; D001835:Body Weight; D003094:Collagen; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D005355:Fibrosis / Q000517:prevention & control; D006339:Heart Rate; D006439:Hemodynamics; D007150:Immunohistochemistry; D007155:Immunologic Factors; D019409:Interleukin-15 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D014760:Viral Fusion Proteins
D007155:Immunologic Factors; D019409:Interleukin-15; D014760:Viral Fusion Proteins; D003094:Collagen