Failure of treatment with interleukin-2 receptor-specific monoclonal antibody in acute coxsackievirus B3 myocarditis in mice.
T cell activation is assumed to play a crucial role in many viral infections. An important marker for the activation of T cells is the interleukin-2 receptor (IL-2R); resting T lymphocytes do not bear detectable amounts of IL-2R. AMT13, a rat monoclonal antibody against mouse IL-2R, inhibits interleukin-2-dependent cell growth both in vitro and in vivo. Therefore, to clarify the effects of anti-IL-2R antibody treatment upon coxsackievirus B3 (CB3)-infected C3H/He mice, AMT13, 1 microg/mouse per day, was administered, subcutaneously, starting on day 0 (group 2) in experiment I or on day 7 (group 4) in Experiment II for 7 days, respectively. Groups 1 and 3 were examined as infected controls. In both experiments, there was no significant difference in mortality or in the severity of myocarditis between the treated and the untreated groups. Also, myocardial CB3 titers on day 7 did not differ significantly between groups 1 and 2. In addition, the distribution of activated T cell subsets in the inflamed myocardium was not changed by the treatment, and the paucity of myocardial IL-2R-positive cells was confirmed in all groups. Effects of the antibody treatment were confirmed by a decrease in delayed type hypersensitivity. Although some reports have shown that anti-IL-2R antibody has been successfully applied to ameliorate acute renal graft-versus-host disease, to enhance survival of skin allografts, and to suppress diabetic insulitis, it did not exert a beneficial effect on acute CB3 myocarditis in mice.
Kishimoto
C
C
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Hiraoka
Y
Y
Takada
H
H
Kurokawa
M
M
Ochiai
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000628:therapy*; D029822:Enterovirus B, Human; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000628:therapy* / Q000821:virology*; D009206:Myocardium / Q000276:immunology; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D017211:Treatment Failure
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2