High-throughput screening of brief naturalistic stress-responsive cytokines in university students taking examinations

This study was designed to prospectively examine the impact of a brief naturalistic stressor (academic examination) on salivary/serum cortisol, measures of anxiety and depressive mood, and 50 circulating immune mediators assessed 7 days before, the first day of, and 2 days after the first term examination period (5 days) among 20 male and 6 female medical students (19.7 ± 3.1 years, mean ± SD). Of 42 serum factors detected, repeated measures ANOVA and Bonferroni post hoc testing indicated that concentrations of macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein (MCP)-3, and β-nerve growth factor (β-NGF) were significantly decreased 2 days after finishing examinations, compared with the levels on the first day of examinations (p < 0.05) in association with a concomitant post-examination decreases (p < 0.05) in anxiety and salivary cortisol levels. In contrast, interleukin (IL)-16 was reciprocally increased between the two time points (p < 0.05). However, after correction for multiple comparisons, only changes in MIF were significant (p < 0.05/42 = 0.00119), and MIF levels peaked on the first day of examinations was significantly higher than those measured both 7 days before and 2 days after the examination. The present high-throughput analysis with multiplex cytokine panels reconfirms the impact of brief naturalistic stressors on immune outcomes, and suggests a potential role of MIF in the acute stress response.