Paclitaxel acts as an adjuvant to promote both Th1 and Th2 immune responses induced by ovalbumin in mice.
Paclitaxel, a diterpenoid isolated from the bark of the Taxus cuspidate cv. Nana, was evaluated for its adjuvant effect on the immune responses in a mouse model. Fifty-six mice were randomly distributed into seven groups with 8 mice in each. Animals were subcutaneously immunized on days 1 and 21 with 100microg of paclitaxel, 10microg of ovalbumin (OVA), OVA with paclitaxel (50, 100 or 200microg) or with aluminum hydroxide (alum). Two weeks after the primary and boost immunizations, blood samples were collected for measurement of serum antibodies. Splenocytes were separated for detection of lymphocyte proliferation in responses to concanavalin A (Con A), lipopolysaccharide (LPS) and OVA, and mRNA expression of Th1 cytokines (IFN-gamma and IL-12), Th2 cytokines (IL-10 and IL-5) and transcription factors T-bet/GATA-3 (Th1/Th2 switcher). Results showed that coadministration of OVA with paclitaxel induced significantly higher IgG, IgG1, IgG2a, IgG2b, IgG3 and IgM responses than when OVA was used alone. In addition, up-regulated T-bet/GATA-3 together with significantly increased mRNA expression of IL-4, IL-10, IFN-gamma and IL-12 by splenocytes, as well as the proliferative responses of splenocytes to Con A, LPS and OVA were observed in paclitaxel-adjuvanted groups. Incubation of a murine macrophage-like cell line with paclitaxel significantly increased TNF-alpha and -10 released from the cells and expression of microRNAs such as miR-155, miR-147, miR-146a and miR-132. Therefore, paclitaxel activated both Th1 and Th2 responses. Considering its unique adjuvant effect demonstrated in this study and a safe record clinically used as an antineoplastic agent, paclitaxel could be an ideal adjuvant candidate when mixed Th1/Th2 immune responses are needed.
Yuan
Lin
L
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310029, China.
Wu
Lihua
L
Chen
Jian
J
Wu
Qiang
Q
Hu
Songhua
S
D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000276:immunology*; D017239:Paclitaxel / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000276:Adjuvants, Immunologic; D050990:GATA3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D010047:Ovalbumin; D017239:Paclitaxel