Modulation of mucosal and systemic immunity by intranasal interleukin 12 delivery.
Interleukin-12 (IL-12) is an important mediator of both cell-mediated and humoral immunity. We have now utilized a noninvasive intranasal (i.n.) delivery system to evaluate the ability of IL-12 to modulate both mucosal and systemic components of the immune system. Mice immunized i.n. with dinitrophenyl conjugated to ovalbumin (DNP-OVA) in combination with cholera toxin B subunit and IL-12 were found to have elevated levels of IFN-gamma and IL-10 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 of bronchoalveolar lavage fluid after IL-12 treatment revealed a significant increase in IgG2a and unaltered IgG1 and IgA anti-OVA antibody levels. Serum IgG2a, IgG2b and IgG3 anti-DNP antibody levels were significantly increased 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 administration. Delivery of IL-12 i.n. also enhanced faecal IgG2a and suppressed IgA levels, in contrast to parenteral treatment which increased both faecal IgG2a and IgA antibody expression. These results provide evidence that i.n. IL-12 treatment can effectively modulate antigen-specific immune responses and enhance immunization strategies for mucosal vaccines.
Arulanandam
B P
BP
Department of Microbiology and Immunology, Medical College of Ohio, Toledo 43614-5806, USA. dmetzger@mco.edu
Metzger
D W
DW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D005243:Feces; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D018664:Interleukin-12 / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology