Interleukin-1 beta, but not interleukin-1 alpha, is required for T-cell-dependent antibody production

Interleukin-1 (IL-1) consists of two molecules, IL-1 alpha and IL-1 beta, a nd IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of these molecu les. Although the adjuvant effects of exogenously administered IL-1 in the humoral immune response are well known, the roles of endogenous IL-I and th e functional discrimination between IL-1 alpha and IL-1 beta have not been elucidated completely. In this report, we investigated the role of IL-I in the humoral immune response using gene-targeted mice. Both primary and seco ndary antibody production against T-dependent antigen, sheep red blood cell s (SRBC), was significantly reduced in IL-1 alpha/beta (-/-) mice, and was enhanced in IL-1Ra(-/-) mice. The intrinsic functions of B cells, such as a ntibody production against type 1 T-independent antigen, trinitrophenyl-lip opolysaccharide and proliferative responses against mitogenic stimuli, were normal in IL-1 alpha/beta (-/-) mice. The proliferative response of T cell s and cytokine production upon stimulation with anti-CD3 monoclonal antibod y were also normal, as was the phagocytotic ability of antigen-presenting c ells (APCs). However, SRBC-specific proliferative response and cytokine pro duction of T cells through the interaction with APCs were markedly impaired in IL-1 alpha/beta (-/-) mice, and enhanced in IL-1Ra(-/-) mice. Moreover, we show that SRBC-specific antibody production was reduced in mice, but no t in IL-1 alpha (-/-) mice. These results show that endogenous IL-1 beta, b ut not IL-1 alpha, is involved in T-cell-dependent antibody production, and IL-1 promotes the antigen-specific T-cell helper function through the T-ce ll-APC interaction.