GP modulated the TSST-1-induced IL-1β/IL-1RA ratio towards an anti-inflammatory phenotype
In a simplified approach, IL-1β and IL-1RA might represent two sides of a coin, i.e. pro- or anti-inflammatory action. Therefore, we applied the IL-1β/IL-1RA ratio as an indicator of the degree of inflammation. Both, LPS and GP + LPS treatments resulted in generating more IL-1β than IL-1RA at early time points, i.e. up to 24 h. Comparing LPS vs. GP + LPS, we did not find substantial alterations over a time course of 48 h in the IL-1β/IL-1RA ratio, only a – non-significant – 2.5fold higher ratio at 6 h. With respect to TSST-1 or the theoretical value of GP/TSST-1 calc. vs. GP + TSST-1, we observed a pronounced anti-inflammatory action of GP, as demonstrated by an about 10–100 fold reduced ratio at 18 h and 24 h of incubation, i.e. a higher production of IL-1RA than of IL-1β (n = 3; both p < 0.05; Fig. 6). A biological relevance of this result was suggested by a decrease of the IL-1 dependent release of IL-2 from murine EL-4 cells following GP + TSST-1 when compared to TSST-1 or GP/TSST-1 calc. (data not shown in detail, n = 4; p < 0.07).
Figure 6  Decreased IL-1β/IL-1RA ratio following GP + TSST-1 when compared to TSST-1. Time course (48 h) of the IL-1β/IL-1RA ratio following incubation of human PBMC with LPS, TSST-1, GP + LPS, GP/LPS calc., GP + TSST-1 or GP/TSST-1 calc. LPS and GP + LPS treatments resulted in generating more IL-1β than IL-1RA up to 24 h. When comparing LPS or GP/LPS calc. vs GP + LPS we did not find significant alterations in the IL-1β/IL-1RA ratio over 48 h. With respect to TSST-1 or GP/TSST-1 calc. vs GP + TSST-1 we observed a pronounced anti-inflammatory action of GP, as demonstrated by an about 10–100 fold reduced ratio at 18 h and 24 h, i.e. a higher production of IL-1RA than of IL-1β (* = p < 0.05). Data are shown as mean ± SEM (n = 3).