INTERLEUKIN-12 ALTERS THE ISOTYPE-RESTRICTED ANTIBODY-RESPONSE OF MICE TO HEN EGG-WHITE LYSOZYME

Protein antigens elicit humoral responses in mice that consist predomi nantly of IgG1 antibodies, We have now investigated the ability of IL- 12, a cytokine reported to augment IgG2a anti-hapten responses through activation of T(h)1 cells, to alter antibody responses to hen eggwhit e lysozyme (HEL), The normal response of BALB/c mice to HEL is highly restricted to IgG1 expression and therefore provides an excellent syst em for determining effects of cytokines on expression of other isotype s, Seven days after immunization, IL-12-treated mice demonstrated grea tly elevated HEL-specific IgG2a antibody levels and suppressed IgG1 pr oduction, while PBS-treated control mice showed a typical IgG1-restric ted response, On day 28, IL-12-treated mice showed heightened serum an tibody levels of both isotypes, Delaying cytokine treatment until afte r the typical IgG1 anti-HEL response had already been established also led to significant elevation of serum IgG2a antibody levels, These ef fects correlated with increased IFN-gamma production; however, adminis tration of IL-12 plus anti-IFN-gamma had little influence on IgG2a enh ancement, although it did relieve the early IgG1 suppression, Furtherm ore, the differential effects of IL-12 on isotype expression did not c orrelate with time; in fact, IgG2a enhancement correlated with loss of IgG1 suppression. Our findings indicate that (i) IL-12 reproducibly i nduces large amounts of IgG2a HEL-specific antibodies in vivo; (ii) it can alter isotype profiles of both primary and secondary responses; a nd (iii) its effects on humoral immunity are not completely explained by induction of T(h)1 cell-derived IFN-gamma.