Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes

Abstract

High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.

Figure 1

Differential expression patterns of inflammation factors by antibody array. (a, b) Array signals were scanned with an ImageQuant LAS4000 scanner, and signal values were statistically analyzed by Student's t-test. Differentially expressed inflammatory factors are shown by boxplots for comparisons with p values less than 0.05. The center line in the boxplots indicates the median for each data set. (c) Boxplot display of inflammation factors differentially expressed between PC and PUC. (d) Line chart of the six inflammatory factors differentially expressed among the four groups. Each line represents the level change of one of the six inflammation factors among the PC, PUC, eHAPC, and cHAPC groups. (e) The array profiles of the six inflammatory factors differentially expressed among the four groups. Each factor was measured in duplicate. Colored boxes indicate the locations of the six significantly different proteins on the arrays, and different colored boxes represent different cytokines. (f) The array data of these six inflammatory factors from the four groups are shown as a heat map, which was analyzed by Cluster 3.0 software. The levels of these proteins are represented by different colors. Low concentrations are in green, median concentrations are in black, and high concentrations are in red.

Figure 2

Differential expression profiles of IL-16 and MCP-1 in four groups by ELISA. The levels of IL-16 and MCP-1 in the serum from HAPC patients and control were detected by ELISA. Values were statistically analyzed by Student' t-test.