| First Author | Rose WA 2nd | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 13146 | PubMed ID | 26272855 |
| Mgi Jnum | J:236437 | Mgi Id | MGI:5806048 |
| Doi | 10.1038/srep13146 | Citation | Rose WA 2nd, et al. (2015) IL-33 released by alum is responsible for early cytokine production and has adjuvant properties. Sci Rep 5:13146 |
| abstractText | Human vaccines have used aluminium-based adjuvants (alum) for >80 years despite incomplete understanding of how alum enhances the immune response. Alum can induce the release of endogenous danger signals via cellular necrosis which elicits inflammation-associated cytokines resulting in humoral immunity. IL-33 is proposed to be one such danger signal that is released from necrotic cells. Therefore, we investigated whether there is a role for IL-33 in the adjuvant activity of alum. We show that alum-induced cellular necrosis results in elevated levels of IL-33 following injection in vivo. Alum and IL-33 induce similar increases in IL-5, KC, MCP-1, MIP-1alpha and MIP-1beta; many of which are dependent on IL-33 as shown in IL-33 knockout mice or by using an IL-33-neutralizing recombinant ST2 receptor. Furthermore, IL-33 itself functions as an adjuvant that, while only inducing a marginal primary response, facilitates a robust secondary response comparable to that observed with alum. However, IL-33 is not absolutely required for alum-induced antibody responses since alum mediates similar humoral responses in IL-33 knockout and wild-type mice. Our results provide novel insights into the mechanism of action behind alum-induced cytokine responses and show that IL-33 is sufficient to provide a robust secondary antibody response independently of alum. |
