Psychological Stress Exerts Effects on Pathogenesis of Hepatitis B via Type-1/Type-2 Cytokines Shift toward Type-2 Cytokine Response

BACKGROUND Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV) infection, little is known about whether and how stress exerts an effect on the course of hepatitis B. METHODS Eighty patients with chronic hepatitis B(CHB) completed the Perceived Stress Scale-10(PSS-10) and State-Trait Anxiety Inventory(STAI). Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at -80 °C were thawed for cytokines, alanine aminotransferase (ALT), and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared. RESULTS Firstly, a negative association between ALT and stress (t =  -4.308; p =  .000), state anxiety (t =  -3.085; p =  .003) and trait anxiety (t =  -4.925; p =  .000) were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10) level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000), and type-1 cytokine interferon-gamma (IFN-γ) level shown a decreased tendency in high stress group (t =  -1.702; p = 0.093). Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t =  -4.606; p = 0.000), state anxiety(t =  -5.126; p = 0.000) and trait anxiety(t =  -4.670; p = 0.000) groups relative to low counterparts. CONCLUSION Our data show stress is not related to the lymphocyte cells count in CHB patients, however, stress induces a shift in the type-1/type-2 cytokine balance towards a type-2 response, which implicated a role of psychological stress in the course of HBV related immune-pathogenesis.