The Eco-logics of Inflammation
Using biomarkers from finger-stick blood spot samples and data from around the globe, IPR biological anthropologist Thomas McDade is revolutionizing the way population-based biological data is collected and studied. Current understandings of inflammation and disease are based almost exclusively on research conducted in clinical settings in affluent industrialized populations. He, however, conducts his research in diverse community-based settings around the world, particularly in the Amazon Basin and Southeast Asia, and also includes U.S. sites.
McDade, who is director of IPR’s Cells to Society (C2S): The Center on Social Disparities and Health, uses this comparative perspective to try to understand how the circumstances in which people live their everyday lives affect their health and physiology. Specifically, he looks at how social and physical environments contribute to variation in human health and affect immune function and inflammation, which contribute to the risk for disease.
Recently, McDade and his colleagues reported that concentrations of C-reactive protein (CRP)—a protein in the blood whose levels rise as part of the inflammatory response—were much lower in adults living in the Philippines or the Ecuadorian Amazon. In contrast, about one-third of adults in the United States have chronically elevated CRP. Acute elevations in CRP are important for protecting us against infectious disease, but when CRP is chronically produced, it is associated with diseases like diabetes, dementia, and cardiovascular disease.
“In my mind, the study underscores the value of an ecological approach to research on the immune system, and it may have significant implications for our understanding of the links between inflammation and chronic disease,” McDade said.
In addition, adults in the Philippines with the lowest CRP were exposed to more infectious microbes when they were infants. Since the overall level of exposure to microbes in infancy is higher in the Philippines and Ecuador than in the United States, McDade's findings raise the intriguing possibility that the increasing global rates of cardiovascular disease and diabetes might be due, in part, to hygiene regiments that have reduced the intensity and diversity of microbial exposures to levels not experienced previously in the history of human species.
In another, more recent study, McDade and his colleagues, including IPR anthropologist Christopher Kuzawa, took the data one step further. They considered whether and to what extent early childhood environments, which are often overlooked by studies conducted in the more affluent, industrialized West, can affect stress and CRP levels in adults. Again using data from the Philippines, the researchers confirmed previous findings that childhood adversity (i.e., extended parental absence) and perceived stress in adulthood both show up as higher levels of CRP in the adults. However, they found one striking difference—for those individuals exposed to more microbes in their infancy and childhood, these exposures did not affect their CRP levels as adults. This suggests a protective effect offered by such microbial exposure against the pro-inflammatory effects of stress in adulthood—an effect missing from more hygienic environments like those in highly industrialized countries.
In terms of population health, McDade said all of these findings suggest that the association between inflammation and cardiovascular disease frequently reported in the United States may only apply in ecological settings characterized by low levels of exposure to infectious disease.
“It builds on research on chronic inflammation and cardiovascular disease in the United States and other affluent, industrialized settings and suggests that patterns seen here may not apply globally,” McDade said. “It also suggests that the levels of chronic inflammation we see in the United States are not universal, and may be a product of epidemiological transitions that have lowered our level of exposure to infectious microbes.”
These research projects were part of the Shuar Health and Life History Project and the Cebu Longitudinal Health and Nutrition Survey, and were funded by the National Science Foundation.
Thomas McDade is professor of anthropology, Director of IPR's Cells to Society (C2S): The Center on Social Disparities and Health, and an IPR fellow.
Reporting for this article also came from the Office for Research 2011 Annual Report and “Rethinking Links Between Inflammation, Chronic Disease” by Hilary Hurd Anyaso. Photo: Mary Hanlon.
McDade, T.W., M. Hoke, J. Boria, L. Adair, and C. Kuzawa. In press. Do environments in infancy moderate the association between stress and inflammation in adulthood? Initial evidence from a birth cohort in the Philippines. Brain, Behavior, and Immunity.
McDade, T.W., P. Tallman, F. Madimenos, M. Liebert, T. Cepon, L. Sugiyama, and J. Snodgrass. 2012. Analysis of variability of high sensitivity C-reactive protein in lowland Ecuador reveals no evidence of chronic low-grade inflammation. American Journal of Human Biology 24(5): 675-81.
McDade, T.W., J. Rutherford, L. Adair, and C. Kuzawa. 2010. Early origins of inflammation: Microbial exposures in infancy predict lower levels of C-reactive protein in adulthood. Proceedings of the Royal Society B 277: 1129-37.
McDade, T.W., J. Rutherford, L. Adair, and C. Kuzawa. 2009. Population differences in associations between C-reactive protein concentration and adiposity: Comparison of young adults in the Philippines and the United States. American Journal of Clinical Nutrition 89(4): 1237-45.