In vivo effects of anticytokine antibodies on isotype restriction in Mesocestoides corti-infected BALB/c mice.

Chronic infection of mice with the cestode Mesocestoides corti results in an antibody response restricted to immunoglobulins M (IgM) and G1 (IgG1). To determine which of the known lymphokines are involved in the restricted isotype response, we treated M. corti-infected mice with a panel of anticytokine monoclonal antibodies against interleukin-4 (IL-4), IL-5, IL-6, and gamma interferon. The effects of anti-IL-4 were of particular importance, since IL-4 is known to enhance IgG1 production and an IgG1 response predominates in infected animals. Interestingly, injection of anti-IL-4 alone had no effect on IgG1 levels at day 7 postinfection and actually enhanced levels at day 10. Decreases in IgM levels were observed in anti-IL-4-treated mice. Administration of anti-IL-5 inhibited IgM production early in infection, but no effects on IgG1 levels were observed. Treatment of infected mice with anti-gamma interferon had no effect on any of the isotypes analyzed. Treatment of infected mice with anti-IL-6 antibody had the most dramatic effects, with inhibition of IgM and IgG1 by day 14 of infection. The transient expression of IgG3, which is sometimes observed very early in the infection process, was also inhibited by anti-IL-6, suggesting that the inhibition observed was not isotype specific. To determine whether cytokines were acting in concert to effect the high IgM and IgG1 levels in infected animals, anticytokine antibodies were also injected in combinations. However, the only combinations that inhibited IgG1 levels contained anti-IL-6, and the extent of inhibition was not greater than that of anti-IL-6 alone. Results are discussed in terms of the effects of cytokines on parasite-induced isotype expression and the potential for IL-4-independent mechanisms of IgG1 production.