| . Early evolutionary pressures derived from human interactions with pathogens, predators and human conspecifics (such as rivals) resulted in an inflammatory bias that included an integrated suite of immunological and behavioural responses that conserved energy for fighting infection and healing wounds, while maintaining vigilance against attack. This inflammatory bias is believed to have been held in check during much of human evolution by exposure to minimally pathogenic, tolerogenic organisms in traditional (that is, rural) environments that engendered immunological responses characterized by the induction of regulatory T (TReg) cells, regulatory B (BReg) cells and immunoregulatory M2 macrophages as well as the production of the anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGFβ). In modern times, sanitized urban environments of more developed societies are rife with psychological challenges but generally lacking in the types of infectious challenges that were primary sources of morbidity and mortality across most of human evolution. In the absence of traditional immunological checks and balances, the psychological challenges of the modern world instigate ancestral immunological and behavioural repertoires that represent a decided liability, such as high rates of various inflammation-related disorders including depression