Cytokine responses to recombinant cholera toxin B subunit produced by Bacillus brevis as a mucosal adjuvant

We attempted to clarify the mechanism of the mucosal adjuvanticity of recom binant cholera toxin B subunit (rCTB), which is inherently uncontaminated w ith the holotoxin produced by Bacillus brevis and has a powerful mucosal ad juvant activity, on cytokine responses compared with that of cholera toxin (CT), rCTB had no ability to stimulate cyclic AMP formation in mouse perito neal macrophages (M Phi). Cytokine production by non-immunized M Phi cultur ed with rCTB or CT and by the spleen cells of mice co-immunized intranasall y with ovalbumin (OVA) and rCTB or CT was examined. rCTB alone did not indu ce interleukin (IL)-1 alpha/beta or IL-6 production by M Phi, but combinati on of rCTB with lipopolysaccharide (LPS) enhanced both IL-1 alpha/beta prod uction. Conversely, CT plus LPS suppressed IL-1 alpha/beta production more than LPS alone. Both rCTB and CT suppressed IL-12 secretion induced by inte rferon gamma (IFN gamma) plus LPS. IL-2, IL-4, IL-5, and IL-10 were secrete d by mouse spleen cells restimulated with OVA after intranasal co-administr ation of OVA together with rCTB, and in response to CT, the same cytokines were secreted. The different effect of rCTB on M Phi from that of CT may me an a difference between the mechanisms of rCTB and CT during the early stag e of an immune response.