Regulation of cytokine gene expression by adjuvants in vivo.
Antibody isotype affects biological activity of the antibodies and therefore should be considered in prevention of disease by vaccination. In previous reports, we demonstrated that adjuvants affect the antibody isotype switching process and favour the production of certain isotypes. The present study extends these findings and shows fundamental differences in the cytokine induction pattern according to the adjuvant used. Cytokine mRNA levels were determined by in situ RNA-RNA hybridization performed on splenocytes isolated from mice injected with different adjuvants. The results revealed that Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), Al(OH)3 and QuilA administration results in a type-2 (humoral) response, increasing IL-4, IL-5 and IL-13 gene expression, while poly I:C exhibits a type-1 (cell-mediated) response, increasing the production of interferon-gamma (IFN-gamma), IL-2 and IL-6 mRNA. Finally, BeSO4 and poly A:U augment IL-5 and IL-6 mRNA production, while lipopolysaccharide (LPS) and LiCl augment IL-6 and tumour necrosis factor-alpha (TNF-alpha) mRNA production. Also, the adjuvants appear capable of overcoming the inherent IL-2/IFN-gamma and IL-4 dichotomy of C57B1/6 and BALB/c mice, respectively, in response to cellular antigens such as Leishmania and herpes simplex virus (HSV). The overall data suggest that adjuvants direct the isotype switching process via induction of certain cytokines, a finding that can be useful in selection of the most efficient isotype of protective antibodies for disease prevention by vaccination.
Victoratos
P
P
Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Greece.
Yiangou
M
M
Avramidis
N
N
Hadjipetrou
L
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D001608:Beryllium / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007369:Interferon Inducers / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D018021:Lithium Chloride / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011063:Poly A-U / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D062605:Quillaja Saponins; D012333:RNA, Messenger / Q000378:metabolism; D012503:Saponins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007369:Interferon Inducers; D007378:Interleukins; D008070:Lipopolysaccharides; D062605:Quillaja Saponins; D012333:RNA, Messenger; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; C020711:beryllium sulfate; D011063:Poly A-U; D000536:Aluminum Hydroxide; C046386:Quil A; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D018021:Lithium Chloride; D011070:Poly I-C; D001608:Beryllium