Infectious diseases, IL6 −174G > C polymorphism, and human development

• Adaptation to pathogens selected for high-producing proinflammatory cytokine alleles.
• This adaptation increased the risk for neuroinflammation and its behavioral sequelae.
• Global variability in IL6 allele frequencies follows geographic clines.
• These geographic clines reflect pathogen prevalence and related behavioral phenotypes.
• Evolutionary pressure shaped the long course of human cognitive/social development.

Interleukin-6 (IL6) is a pro-inflammatory cytokine that is required for resistance against many pathogens. However, sustained IL6 activity can cause tissue damage in the periphery and brain. Previous studies have shown that populations in disease-endemic regions adapt by selecting the high-producing G-allele at the −174G > C (rs1800795) polymorphism, while others have linked increased IL6 to cognitive impairments. The present study sought to determine whether up-regulation of IL6 by the G-allele at rs1800795 polymorphism in disease-endemic regions was associated with increased cognitive deficits and corollary reductions in social, economic, and political development.We tested these hypotheses in a global sample of 189 nations with World Health Organization ratings for infectious diseases. We also included the Historical Pathogen Prevalence index, a measure of national average intelligence (IQ), and the United Nation Human Development Index (HDI) including per capita income, life expectancy, child mortality, and fertility rate. IL6 −174G > C allele frequencies were obtained from 171,168 individuals spanning 84 nations.The high-producing G-allele frequency was positively correlated with infectious disease ranking (r = 0.745, P < 0.001) and negatively with IQ (r = −0.524, P < 0.001) and HDI (r = −0.671, P < 0.001). These robust findings suggest that in regions with a high pathogen burden the need for a strong IL6 response is accompanied by cognitive deficits and reduced HDI ranking.