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 recombinant cholera toxin B subunit (rCTB), which is inherently uncontaminated with the holotoxin produced by Bacillus brevis and has a powerful mucosal adjuvant activity, on cytokine responses compared with that of cholera toxin (CT). rCTB had no ability to stimulate cyclic AMP formation in mouse peritoneal macrophages (Mphi). Cytokine production by non-immunized Mphi cultured with rCTB or CT and by the spleen cells of mice co-immunized intranasally with ovalbumin (OVA) and rCTB or CT was examined. rCTB alone did not induce interleukin (IL)-1alpha/beta or IL-6 production by Mphi, but combination of rCTB with lipopolysaccharide (LPS) enhanced both IL-1alpha/beta production. Conversely, CT plus LPS suppressed IL-1alpha/beta production more than LPS alone. Both rCTB and CT suppressed IL-12 secretion induced by interferon gamma (IFN gamma) plus LPS. IL-2, IL-4, IL-5, and IL-10 were secreted by mouse spleen cells restimulated with OVA after intranasal co-administration of OVA together with rCTB, and in response to CT, the same cytokines were secreted. The different effect of rCTB on Mphi from that of CT may mean a difference between the mechanisms of rCTB and CT during the early stage of an immune response.
Maeyama
J
J
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan. meymj@nih.go.jp
Isaka
M
M
Yasuda
Y
Y
Matano
K
K
Kozuka
S
S
Taniguchi
T
T
Ohkuma
K
K
Tochikubo
K
K
Goto
N
N
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D001407:Bacillus; D002772:Cholera Toxin / Q000276:immunology* / Q000302:isolation & purification; D000242:Cyclic AMP / Q000378:metabolism; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D007378:Interleukins; D008070:Lipopolysaccharides; D021122:Protein Subunits; D011994:Recombinant Proteins; D010047:Ovalbumin; D002772:Cholera Toxin; D000242:Cyclic AMP