Evolutionary origins of neuropeptides, hormones, and receptors: possible applications to immunology.

Immune function requires intercellular communication. The vocabulary includes messenger molecules closely linked to the immune system as well as more widely acting messengers such as hormones and neuroactive substances. To try to bring these together, we have used an evolutionary approach. Materials that resemble hormonal peptides and neuropeptides, previously thought to be restricted to multicellular animals, are present in protozoa, bacteria, and higher plants. There is also evidence for substances in microbes that bind hormones and other messengers, which resemble receptors of vertebrates. Therefore, we suggest that the molecules of intercellular communication probably arose much earlier in evolution than the endocrine, nervous, and immune systems. This insight provides new understanding of messenger systems in vertebrates, as applied to the immune system, as well as new insights into possible disease mechanisms, including those that involve autoimmunity.