Objectives: Influenza A viruses play the largest role in the worldwide epidemiology of infectious diseases. We examined the effects of intact type and F(ab')2 type of immunoglobulin preparations on murine influenza A virus myocarditis in mice.
Methods and results: In vitro study showed that intact type and F(ab')2 type of immunoglobulin preparations had antiviral activities against many substrains of influenza A virus and other cardiotropic viruses, and that dose-dependent suppression of an influenza A virus (NWS type) was demonstrated by the treatment of both intact immunoglobulin and F(ab')2 fragments of immunoglobulin. The dose inhibiting 50% of plaques was same between intact type and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2 fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2 (MIP-2) production in influenza A virus infected macrophages in vitro, which is a murine counterpart of interleukin-8. This suppression of MIP-2 production by intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma III/II receptor) antibody pretreatment. Intact immunoglobulin (1 g/kg/day) or F(ab')2 fragments of immunoglobulin (1 g/kg/day) were administered to the virus-inoculated A/J mice intraperitoneally daily, starting simultaneously with virus inoculation (Experiment I ) and 2 days after the virus inoculation (Experiment II ), until 10th days after virus inoculation. In Experiment I, survival was higher in treated [intact (100%, 20/20), and F(ab')2 (100%, 20/20)] than in control (25%, 5/20) mice; intact type and F(ab')2 type immunoglobulin administration completely suppressed the development of myocarditis. In Experiment II, survival rate was significantly higher (75%, 15/20) and myocarditis was less severe in intact immunoglobulin treated mice, but not in F(ab')2 fragment treated mice (60%, 12/20), than in untreated mice (35%, 7/20). Serum neutralizing antibody titers in treated mice were significantly higher compared with untreated mice in Experiments I and II. In addition, serum MIP-2 concentrations in intact immunoglobulin treated mice, but not in F(ab')2 fragments treated mice, were lower compared with untreated mice in Experiment II. Immunoglobulin therapy suppresses influenza A virus myocarditis by increasing neutralizing antibody titers and the suppression of myocardial virus activities. From the stand-point of suppression of MIP-2 concentrations, intact type is superior to F(ab')2 type.
Conclusions: Immunoglobulin treatment may be promising for the prevention of influenza A virus myocarditis.