Prevention of anti-T-cell receptor alpha beta monoclonal antibody-induced side-effects by treatment with cyclosporin A without interference of monoclonal antibody-induced immunosuppression in mice.
Anti-T-cell receptor (TCR)alpha beta monoclonal antibody (mAb; H57-597) injection in mice caused cytokine (tumour necrosis factor and interferon-gamma) release and clinical side-effects such as piloerection and body weight loss similar to anti-CD3 mAb (145-2C11) injection. Treatment with cyclosporin A (CsA) for 3 days, from day -2 to day 0, prior to anti-TCR alpha beta mAb injection almost completely abolished the mAb-induced cytokine release, and completely inhibited the mAb-induced body weight loss. Furthermore, treatment with CsA from day -2 to day 0 did not inhibit the mAb-induced in vivo immunosuppressive effects, i.e. prolongation of skin allograft and T-cell depletion in the periphery. These results indicate that CsA treatment prior to mAb treatment could effectively inhibit the mAb-induced side-effects without interference of the mAb-induced in vivo immunosuppression. From these results, we propose that CsA treatment prior to injection of anti-TCR alpha beta mAb may be recommended to reduce mAb-induced side-effects.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D007108:Immune Tolerance / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D015431:Weight Loss / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine