Interleukin-18 plays a role in both the alum-induced T helper 2 response and the T helper 1 response induced by alum-adsorbed interleukin-12.
Previous studies have shown that the antigen-specific T helper 2 (Th2) response induced by alum adjuvants is interleukin (IL)-4 independent. As a role for IL-18 in Th2 induction has recently been described, in addition to its role in enhancing Th1 responses, we have studied the Th2 response induced by ovalbumin (OVA) adsorbed to alum in wild-type and IL-18-deficient mice. Our results indicate that while endogenous IL-18 facilitates alum-induced IL-4 production, OVA-specific immunoglobulin G1 (IgG1) and IgE production remain unaffected. Furthermore, antigen-specific Th1 responses induced with alum/IL-12-adsorbed OVA were demonstrated to be highly IL-18 dependent. Despite these observations, injection of BALB/c mice with exogenous IL-18 adsorbed to alum/OVA did not alter IL-4 or interferon-gamma production by T cells and had little effect on the relative production of IgG1/IgG2a antibody subclasses compared with alum/OVA inoculated mice. However, the previously described synergism between IL-12 and IL-18 in Th1 induction was evident as the Th1-promoting activity of alum/IL-12 against adsorbed OVA was greatly augmented by the coadministration of IL-18. These results indicate that while alum-induced IL-18 can facilitate Th2 induction, the addition of exogenous IL-18 cannot further enhance the alum-induced Th2 response.
Pollock
Kevin G J
KG
Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow, UK.
Conacher
Margaret
M
Wei
Xiao-Qing
XQ
Alexander
James
J
Brewer
James M
JM
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D020382:Interleukin-18; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; D010047:Ovalbumin