Immunopharmacology of CpG oligodeoxynucleotides and ribavirin

Abstract

To investigate their potential mechanisms of action, the nucleoside analogue ribavirin and a TLR9 agonist were compared. The CpG oligodeoxynucleotides (ODN) demonstrated strong TLR9-related Th1-type effects, and ribavirin appeared only to mediate signaling in TLR-transfected cells. CpG ODN represent a promising new type of therapeutic drug for hepatitis C or other infectious diseases.

FIG. 1.

Ribavirin does not induce secretion of IFN-α, IL-10, or IFN-γ from human PBMC. Mean cytokine secretion ± the standard error of the mean of three (ribavirin in panel C), four (A and B), or six (C) donors with CpG ODN (2006), control ODN (1982), or LPS (100 ng/ml). Med, medium control. *, P ≤ 0.1; **, P < 0.05 for ODN 2006 compared to medium control (Student's t test; Sigma Plot, SPSS Inc., Chicago, Ill.).

FIG. 2.

IL-6 and IP-10 secretion or B-cell proliferation are induced by CpG ODN. Human PBMC were incubated with CpG ODN (2006), control ODN (5177), ribavirin, or 100 ng of LPS/ml. Data are the mean protein secretion ± the standard error of the mean (SEM) of four donors and the mean percentage ± SEM of proliferating cells of four donors. *, P < 0.1; **, P < 0.05 (see Fig. 1 legend for further information).

FIG. 3.

Ribavirin affects SEB-mediated IL-5 production. Mean IL-5 secretion ± standard error of the mean of five (A) or three (B) donors. *, P ≤ 0.2; **, P < 0.1 compared to SEB. The lower detection limit of the IL-5 ELISA was 4 pg/ml.

FIG. 4.

Ribavirin stimulates NF-κB activation in TLR7 and TLR8 transfectants. Stimulation indices ± standard deviations of NF-κB activation of one representative experiment out of two experiments are shown.