Interleukin 12 alters the isotype-restricted antibody response of mice to hen eggwhite lysozyme.
Protein antigens elicit humoral responses in mice that consist predominantly of IgG1 antibodies. We have now investigated the ability of IL-12, a cytokine reported to augment IgG2a anti-hapten responses through activation of Th1 cells, to alter antibody responses to hen eggwhite lysozyme (HEL). The normal response of BALB/c mice to HEL is highly restricted to IgG1 expression and therefore provides an excellent system for determining effects of cytokines on expression of other isotypes. Seven days after immunization, IL-12 treated mice demonstrated greatly elevated HEL-specific IgG2a antibody levels and suppressed IgG1 production, while PBS-treated control mice showed a typical IgG1-restricted response. On day 28, IL-12-treated mice showed heightened serum antibody levels of both isotypes. Delaying cytokine treatment until after the typical IgG1 anti-HEL response had already been established also led to significant elevation of serum IgG2a antibody levels. These effects correlated with increased IFN-gamma production; however, administration of IL-12 plus anti-IFN-gamma had little influence on IgG2a enhancement, although it did relieve the early IgG1 suppression. Furthermore, the differential effects of Il-12 on isotype expression did not correlate with time; in fact, IgG2a enhancement correlated with loss of IgG1 suppression. Our findings indicate that (i) IL-12 reproducibly induces large amounts of IgG2a HEL-specific antibodies in vivo; (ii) it can alter isotype profiles of both primary and secondary responses; and (iii) its effects on humoral immunity are not completely explained by induction of Th1 cell derived IFN-gamma.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002645:Chickens; D004527:Egg Proteins / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology
D004527:Egg Proteins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D009113:Muramidase