The innate immune response to infection, toxins and trauma evolved into networks of interactive, defensive, reparative, regulatory, injurious and pathogenic pathways

It is hypothesized that, under selective pressure from infections, trauma and toxins, multicellular organisms evolved an innate immune response (IIR): (1) comprising neural, endocrine, biochemical and cellular pathways that restore homeostasis through pathogen clearance, repair of injury and regulation of inflammation, but also mediate injury and disease; (2) that functions independently of as well as in concert with the adaptive immune response (AIR); (3) whose functions in health and disease depend upon cross-talk and networking among these pathways. A critical review of the literature provides strong evidence to support the evolution of the IIR, Propositions 1 and 2 and partial support for Proposition 3: there are numerous interactions among the mammalian IIR pathways, but there is no direct evidence for more complex functioning networks in vivo. Some implications and questions raised by the hypothesis are presented.