ENHANCEMENT OF INTERLEUKIN-4 PRODUCTION BY PERTUSSIS TOXIN

Pertussis toxin (PT), a protein toxin Of Bordetella pertussis, has man y biological activities, including potent adjuvant capacity and the ab ility to up-regulate immunoglobulin E (IgE) production. Interleukin-4 (IL-4) is a cytokine which is essential for the IgE response. Accordin gly, we examined the effect of PT on IL-4 Production. Spleen and lymph node cell suspensions were prepared from immunized mice and cultured with antigen or polyclonal stimuli in vitro. IL-4 secretion was assess ed by bioassay, and IL-4 mRNA expression was assessed by reverse trans cription and polymerase chain reaction. Significantly larger amounts o f IL-4 protein and mRNA were produced in vitro by cells from mice give n PT at the time of immunization than by cells from mice given antigen alone, PT alone, or the combination of antigen with cyclophosphamide. Total and antigen-specific serum IgE levels were significantly elevat ed in immunized mice given PT, compared with the other groups. Thus, t here was a relationship between serum IgE and IL-4 production. The adm inistration of a single dose of an anti-ILA monoclonal antibody in viv o, at the time of immunization and treatment with PT, abolished the de velopment of the IgE response. These results indicate that PT is a pot ent stimulus for the production of IL-4, which is required for the adj uvant effect of PT on IgE formation.