Regulation by cytokines of eosinophilopoiesis and immunoglobulin E production in mice.

Certain clinical disorders are associated with eosinophilia and hyperimmunoglobulinaemia of the immunoglobulin (Ig) E class, but others give rise to eosinophilia without hyperimmunoglobulinaemia. To investigate why there are two such patterns, we immunized BALB/c mice with ovalbumin plus tetanus toxid with aluminium hydroxide gel (alum) as adjuvant, which caused eosinophilopoiesis and hyperimmunoglobulinaemia, and also immunized mice with the same antigens and complete Freund's adjuvant (CFA), which caused only eosinophilopoiesis. The difference in the adjuvant brought about the two different patterns. Monoclonal antibodies to four cytokines were used to find that eosinophilopoiesis was mediated by interleukin-5 (IL-5), whichever the adjuvant, and that IgE production in mice treated with alum was regulated by both IL-4 and IL-5. The lack of increase in IgE production was not due to suppression by interferon-gamma (IFN-gamma) or by CD8+ T cells. By the polymerase chain reaction, both IL-4 and IL-5 mRNA were detected in cells from mice given alum, but only IL-5 mRNA was found in cells from mice given CFA. Thus, alum used as the adjuvant resulted in both eosinophilopoiesis and IgE production, but CFA resulted in eosinophilopoiesis alone. The dissociation between eosinophilopoiesis and IgE production shown in the mice given CFA could be due to the dissociation between the expression of mRNA of the cytokines IL-4 and IL-5 in vivo.