Pro-inflammatory, chemotactic, and anti-inflammatory cytokine responses associate with HPA, but not SNS, function in lung cancer patients

Abstract

Disrupted cortisol rhythms are associated with earlier mortality across a number of cancer types; however, immune mechanisms by which circadian disruption may accelerate tumor progression have not been adequately defined in humans. Using blood samples from 62 lung cancer patients, PBMC were incubated with stimulators of acquired and innate immunity (PHA, LPS), and cytokines were measured. Serum DHEA, diurnal salivary cortisol, and overnight urinary catecholamines were collected. Hypothesized associations between stimulated analytes (pro-inflammatory: IL-1β, IL-6, TNF-α, IL-17; chemotactic: eotaxin; anti-inflammatory: IL-10; Type 1/TH1: IFN-γ; Type 2/TH2: IL-13, IL-5) and endocrine disruption (HPA axis: DHEA, cortisol; SNS: epinephrine, norepinephrine) were examined using linear regressions. Increased release of eotaxin in unstimulated control (p = 0.030) and LPS (p = 0.025) was associated with dysregulated diurnal cortisol, while increased release of IL-10 stimulated in LPS (p = 0.018) was associated with higher mean cortisol secretion. When adjusting for unstimulated controls, an increased release of IL-6 stimulated in PHA (p = 0.021) and IL-10 stimulated in LPS (p = 0.019), was associated with higher mean cortisol secretion. Response to an immune challenge was associated with HPA axis disruption, but not markers of SNS function. These findings suggest immune mechanisms may partly explain the prognostic significance of HPA axis dysregulation in patients with lung cancer.