Evolutionary adaptation of inflammatory immune responses in human beings.

Modern man's ancestors lived in an environment where infectious, tropical diseases would have been endemic. We postulate that this relatively hostile environment would have caused genetic selection for increased proinflammatory immune responses. On migrating to temperate regions, pronounced proinflammatory responses would have been less important and selected against due to increased mortality from overly vigorous responses to harmless environmental agents. This hypothesis is supported by the observation that proinflammatory alleles in several genes involved in inflammation are more prevalent in populations with long-term tropical ancestry than those with long-term residence in temperate regions. In addition, when the former populations relocate from a tropical to a temperate region, they have a higher incidence of allergic inflammatory diseases than the latter populations. These observations suggest that there may be general patterns of recent evolutionary adaptation of the human immune system to particular regions and that these adaptations can produce differences in disease susceptibility.