Role of interleukin-1 receptor antagonist in regulating specific Hepatitis B antibody production (IRM12P.646)

Abstract While exogenous interleukin-1 beta was reported to facilitate antibody production, the function and mechanism of its conventional suppressor interleukin-1 receptor antagonist (IL-1Ra) in regulating specific antibody remain largely unknow. We showed that, upon aluminium-conjugated commercial hepatitis B surface antigen vaccination, hepatitis B antibody response was considerably amplified in IL-1Ra-/- mice, demonstrated by higher HBsAb level, increased germinal center and HBsAb secreting B cell numbers in dLN but not spleen. Mechanismly, IL-1 signalling pathway was, unexpectedly, found not to be involved in the process, evident by equivalent HBsAb titre in nalp3-/-, caspase-1-/- and IL-1R-/- mice as in wt. Surprisingly, the IL-17 production was amplified in IL-1Ra-/- mice, demonstrated by higher serum IL-17 level and higher number and frequency of IL-17 secreting cells in dLN of IL-1Ra-/- mice. Moreover, HBsAb level in IL1rn-/- x IL17-/- mice was comparable to that in wt mice, suggesting the essential role of IL-17 in regulating the elevated HBsAb level in IL-1Ra-/- mice. Furthermore, CD4 T cells was identified as the main source of IL-17 production in dLN of IL-1Ra-/- mice, indicating the essential role of IL-17 secreting CD4 T cells in upregulating HbsAb production. Therefore, the increased HBsAb production in IL-1Ra-/- was irrelevant to IL-1 pathway but dependend on evelated IL-17. We have thus proposed a novel mechanism of IL-1Ra in regulating specific antibody production.