Early environments and the ecology of inflammation

Abstract

Recent research has implicated inflammatory processes in the pathophysiology of a wide range of chronic degenerative diseases, although inflammation has long been recognized as a critical line of defense against infectious disease. However, current scientific understandings of the links between chronic low-grade inflammation and diseases of aging are based primarily on research in high-income nations with low levels of infectious disease and high levels of overweight/obesity. From a comparative and historical point of view, this epidemiological situation is relatively unique, and it may not capture the full range of ecological variation necessary to understand the processes that shape the development of inflammatory phenotypes. The human immune system is characterized by substantial developmental plasticity, and a comparative, developmental, ecological framework is proposed to cast light on the complex associations among early environments, regulation of inflammation, and disease. Recent studies in the Philippines and lowland Ecuador reveal low levels of chronic inflammation, despite higher burdens of infectious disease, and point to nutritional and microbial exposures in infancy as important determinants of inflammation in adulthood. By shaping the regulation of inflammation, early environments moderate responses to inflammatory stimuli later in life, with implications for the association between inflammation and chronic diseases. Attention to the eco-logics of inflammation may point to promising directions for future research, enriching our understanding of this important physiological system and informing approaches to the prevention and treatment of disease.

Fig. 1.

Hypothetical pattern of CRP production over 8 wk for three individuals according to the acute-phase (Left) and chronic low-grade (Right) approaches to the study of inflammation and disease.

Fig. 2.

Association between microbial exposures in infancy and probability of elevated CRP in young adulthood in the Philippines. Results are based on predicted probabilities from the fully adjusted logistic regression models reported in ref. . Low and high values for predictors were set as follows: diarrhea (zero to three or more episodes), animal feces exposure (zero to three or more intervals), and born in dry season (no or yes). Original values were retained for other variables in the model.

Fig. 3.

Conceptual model of the association between microbial exposure in infancy and regulation of inflammation in adulthood. The arrow from infancy through adulthood represents developmental time. Upper applies to environments with higher levels of microbial exposures; Lower describes low-infection, highly hygienic environments.