Anti-IL-4 treatment at immunization modulates cytokine expression, reduces illness, and increases cytotoxic T lymphocyte activity in mice challenged with respiratory syncytial virus.
Upon respiratory syncytial virus (RSV) challenge, mice previously immunized intramuscularly with inactivated whole virus express a Th2-like pattern of cytokine mRNA, while mice immunized with live virus intranasally express a Th1-like pattern. In this study, we evaluated the effects of anti-IL-4 treatment on the induction of immune responses after immunization. Mice treated with anti-IL-4 at the time of immunization with inactivated RSV had reduced clinical illness after live virus challenge, as measured by weight loss, illness score, and virus replication. This was associated with an augmented CD8+ cytotoxic T lymphocyte (CTL) activity, increased expression of IFN-gamma mRNA relative to IL-4 mRNA, and a higher titer of RSV-specific IgG2a in the anti-IL-4 treated mice before challenge. Anti-IL-4 administration at the time of challenge had no effects on illness, immunoglobulin isotype, or cytokine patterns. These results suggest that inhibition of IL-4 action at immunization can shift the selective activation of lymphocytes to a more Th1-like response. This cytokine milieu is associated with augmented CTL activity, which may be the factor responsible for rapid viral clearance and reduced illness at the time of remote RSV challenge.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605.
Y W
YW
Tang
B S
BS
Graham
D000818:Animals; D000911:Antibodies, Monoclonal; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D005260:Female; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D014765:Viral Vaccines; D015847:Interleukin-4