Profiles of inflammatory markers and their association with cardiometabolic parameters in rural and urban Uganda

Background: Inflammation may be one of the pathways explaining differences in cardiometabolic risk between urban and rural residents. We investigated associations of inflammatory markers with rural versus urban residence, and with selected cardiometabolic parameters previously observed to differ between rural and urban residents: homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), blood pressure (BP) and body mass index (BMI). Methods: From two community surveys conducted in Uganda, 313 healthy individuals aged ≥ 10 years were selected by age- and sex-stratified random sampling (rural Lake Victoria island communities, 212; urban Entebbe municipality, 101). Fluorescence intensities of plasma cytokines and chemokines were measured using a bead-based multiplex immunoassay. We used linear regression to examine associations between the analytes and rural-urban residence and principal component analysis (PCA) to further investigate patterns in the relationships. Correlations between analytes and metabolic parameters were assessed using Pearson’s correlation coefficient. Results: The urban setting had higher mean levels of IL-5 (3.27 vs 3.14, adjusted mean difference [95% confidence interval] 0.12[0.01,0.23] p=0.04), IFN-⍺ (26.80 vs 20.52, 6.30[2.18,10.41] p=0.003), EGF (5.67 vs 5.07, 0.60[0.32,0.98] p<0.00001), VEGF (3.68 vs 3.28, 0.40[0.25,0.56] p<0.00001), CD40 Ligand (4.82 vs 4.51, 0.31[0.12, 0.50] p=0.001) and Serpin-E1 (9.57 vs 9.46, 0.11[0.05,0.17] p<0.00001), but lower levels of GMCSF (2.94 vs 3.05, -0.10[-0.19,-0.02] p=0.02), CCL2 (2.82 vs 3.10, -0.45[-0.70,-0.21] p<0.00001) and CXCL10 (5.48 vs 5.96, -0.49[-0.71,-0.27] p<0.00001), compared to the rural setting. In PCA, the urban setting had lower representation of some classical inflammatory mediators but higher representation of various chemoattractants and vasoactive peptides. HOMA-IR, FBG, BP and BMI were positively correlated with several principal components characterised by pro-inflammatory analytes. Conclusions: In developing countries, immunological profiles differ between rural and urban environments. Differential expression of certain pro-inflammatory mediators may have important health consequences including contributing to increased cardiometabolic risk observed in the urban environment.