Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster

Abstract

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Functional paralysis of human natural killer cells by alphaherpesviruses

“…Additionally, after 2 days of co-culture, VZV exposed NK cells also exhibited suppressed cytokine production, suggesting VZV can affect the efficiency of cytokine expression through several regulatory or inhibitory methods. Recently it was found that NK cells isolated from patients with herpes zoster exhibited significantly lower IFN-γ secretion compared to control subjects, with severity of skin lesion correlated to the degree of IFN-γ suppression [40], corroborating our findings. Reduced IFN-γ and TNF expression upon PMA/I stimulation indicates that VZV and HSV-1 impact points in the cytokine production pathway that are not shared with degranulation, which was unaffected following activation with PMA/I.…”

Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma

“…Given that these patients had advanced disease and were heavily pre-treated, infectious complications could reflect a combination of decreased innate responses and dysfunctional humoral and cell-mediated immunity, already present in these patients. It is well known that NK cells contribute to the defense against herpesviruses, including CMV, HSV-1 and VZV [27,36–39]. NK cells can detect virus infection directly by recognition of viral proteins, and indirectly by binding to molecules that are up-regulated on stressed cells.…”

Risk of cutaneous herpes zoster in patients with spondyloarthritis treated with conventional and biologic disease‐modifying antirheumatic drugs

“…Infliximab downregulated interferon (IFN)‐γ activation by 5.9‐fold but none were evident for etanercept. Since IFN‐γ is a critical factor for enhancement of natural killer activity and inhibition of VZV replication, it was postulated that defective IFN‐γ production may be related to VZV reactivation . Pharmacokinetic differences also play a role.…”

“…Since IFN-γ is a critical factor for enhancement of natural killer activity and inhibition of VZV replication, 30 it was postulated that defective IFN-γ production may be related to VZV reactivation. 31,32 Pharmacokinetic differences also play a role. According to the therapeutic window concept, 33 the steady-state range of serum or tissue drug concentrations should be adequate to neutralize surplus TNF, yet not so high as to threaten host defense.…”