Modulation of mucosal and systemic immunity by intranasal interleukin 12 delivery

Interleukin-12 (IL-12) is an important mediator of both cell-mediated and h umoral immunity. We have now utilized a noninvasive intranasal (i.n.) deliv ery system to evaluate the ability of IL-12 to modulate both mucosal and sy stemic components of the immune system. Mice immunized i.n, with dinitrophe nyl conjugated to ovalbumin (DNP-OVA) in combination with cholera toxin B s ubunit and IL-12 were found to have elevated levels of IFN-gamma and IL-IO mRNA transcripts in both lungs and spleens compared with mice not receiving IL-12. In addition, expression of lung IL-5 mRNA was inhibited. Analysis o f bronchoalveolar lavage fluid after IL-12 treatment revealed a significant increase in IgG2a and unaltered IgG1 and IgA anti-OVA antibody levels. Ser um IgG2a, IgG2b and IgG3 anti-DNP antibody levels were significantly increa sed by IL-12 given i.n., while serum IgG1 antibody levels were suppressed, results that are similar to those seen after systemic antigen plus IL-12 ad ministration. Delivery of IL-12 i.n. also enhanced faecal IgG2a and suppres sed IgA levels, in contrast to parenteral treatment which increased both fa ecal IgG2a and IgA antibody expression. These results provide evidence that i.n. IL-12 treatment can effectively modulate antigen-specific immune resp onses and enhance immunization strategies for mucosal vaccines. (C) 1998 El sevier Science Ltd. All rights reserved.