Complexities of targeting innate immunity to treat infection.

Innate immunity is an ancient form of host defence that is activated rapidly to enable, through a multiplicity of effector mechanisms, defence against a broad spectrum of microbial threats. From this perspective, innate immunity has desirable characteristics of a therapy against infections, and, as a consequence, the innate immune system has become a major target for the development of therapeutics to control inflammation and immune defences. Although advances in the field have come at a furious pace, and several companies are advancing the first Toll-like receptor-based drugs, there remain many unanswered questions about innate immunity and maintaining balance in the immune response. Indeed, innate immunity represents an enormously complex network of molecules, pathways and interactions, controlled by multiple positive and negative regulatory proteins, which are starting to be evaluated in more depth using systems biology approaches. However, accompanying the protective mechanisms is the production of pro-inflammatory cytokines such that, if excessive amplification of innate immunity occurs, there is the potential for such syndromes as sepsis and chronic inflammation.