Cytokines as adjuvants for the induction of mucosal immunity.

Safe nasal vaccines capable of promoting both mucosal and systemic immunity are needed for effective protection against bacterial and viral pathogens. While parenteral cytokine treatment could lead to unwanted toxicity, the nasal delivery route results in low but biologically active serum cytokine levels. Interleukin (IL)-6, IL-1 and IL-12, which promote either Th2- or Th1-type responses, respectively, also enhance systemic immunity to co-administered antigens. The chemoattractants lymphotactin (Lptn), RANTES and defensins also exerted adjuvant activity for systemic immunity when nasally administered with antigens. However, each cytokine or innate factor promoted a distinct pattern of T helper cell responses and corresponding IgG subclass response. Interleukin-12, IL-1, and the chemokines Lptn and RANTES promote mucosal immunity. In contrast, nasal IL-6 and defensins failed to induce mucosal S-IgA Ab responses, suggesting that mechanisms more complex than T cell activation and chemotaxis are required for the development of mucosal immunity after nasal delivery of cytokines.