Inflammatory cytokines and antigen presenting cell activation

Immune responses are stimulated in response to threats against health. In animals, defense against infectious agents, particularly rapidly growing viruses and bacteria, requires an immediate response to limit growth and dissemination, and then stimulation of a more prolonged, specific immunity to prevent re-infection. The process by which animals meet the dual needs of an immediate response to danger and initiation of long-term protection is substantially influenced by inflammatory cytokines produced primarily by macrophages and professional antigen presenting cells (APCs). Inflammatory cytokines mobilize the immune system in response to danger and increase the efficiency of an immune response as effectors of APC function. Here we review the evidence for the involvement of inflammatory cytokines in immune induction and as mediators of APC activity, with a particular emphasis on swine and on the induction of immunity at mucosal surfaces. The vast majority of infections occur at mucosal surfaces of the enteric, respiratory and reproductive tracts, and induction of protective immunity at these sites is particularly challenging. Induction of immunity at mucosal surfaces of the small intestine is greatly facilitated by the oral adjuvant, cholera toxin (CT). CT potentiates inflammatory cytokine and costimulatory molecule expression in macrophages, and stimulates humoral and cell-mediated immune responses both locally and systemically. These observations are consistent with the hypothesis that activation of APCs is a key step in the induction of antigen-specific immunity, and that inflammatory cytokine expression is a hallmark of activated APC function. The efficacy of vaccine adjuvants, particularly in the context of mucosal immunity, may be determined by their ability to induce a controlled inflammatory response in gut-associated lymphoid tissue, characterized by the expression of various costimulatory molecules and inflammatory cytokines. Thus, elucidation of the patterns of inflammatory cytokine expression and features of APC activation will help to facilitate the rational development of more efficacious vaccines.