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Objectives The aim of the study was to: (1) Identify (early in pregnancy) psychosocial and stress-related factors that predict risk of spontaneous preterm birth (PTB, gestational age Study Design This is a prospective cohort study. Relative risk (RR) analyses investigated association between individual factors and PTB. Machine learning-based interdependency analysis (IDPA) identified factor clusters, strength, and direction of association with PTB. A nonlinear model based on support vector machines was built for predicting PTB and identifying factors that most strongly predicted PTB. Results Higher levels of deleterious factors were associated with increased RR for PTB: General anxiety (RR = 8.9; 95% confidence interval [CI] = 2.0,39.6), pain (RR = 5.7; CI = 1.7,17.0); tiredness/fatigue (RR = 3.7; CI = 1.09,13.5); perceived risk of birth complications (RR = 4; CI = 1.6,10.01); self-rated health current (RR = 2.6; CI = 1.0,6.7) and previous 3 years (RR = 2.9; CI = 1.1,7.7); and divorce (RR = 2.9; CI = 1.1,7.8). Lower levels of protective factors were also associated with increased RR for PTB: low happiness (RR = 9.1; CI = 1.25,71.5); low support from parents/siblings (RR = 3.5; CI = 0.9,12.9), and father-of-baby (RR = 3; CI = 1.1,9.9). These factors were also components of the clusters identified by the IDPA: perceived risk of birth complications (p Conclusion These findings represent an important step toward identifying key factors, which can be assessed rapidly before/after conception, to predict risk of PTB, and perhaps other adverse pregnancy outcomes. Quantifying these factors, before, or early in pregnancy, could identify women at risk of delivering preterm, pinpoint mechanisms/targets for intervention, and facilitate the development of interventions to prevent PTB. Key Points

The authors highlight, from a firsthand perspective, Bruce S. McEwen's seminal influence on the field of stress neurobiology and beyond, and how these investigations have yielded important insights, principles and critical questions that continue to guide stress research today. Featured are discussion of: 1) the important inverted-U relationship between stress/glucocorticoids and optimal physiological function, 2) stress adaptation and the role of adaptive stress responses, 3) mechanisms by which the short-term stress response promotes heightened immune function and immunity, and 4) the far reaching impact of the theoretical framework of allostasis and allostatic load-concepts that have created new bridges between stress physiology, biomedical sciences, health psychology and sociology.

Increased inflammation is reported in Major Depressive Disorder (MDD), which may be more pronounced in suicidal subjects. Vitamin D deficiency may drive this pro-inflammatory state due to vitamin D's anti-inflammatory effects.We quantified plasma 25-hydroxyvitamin D (25(OH)D) and inflammatory markers interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and other inflammatory indices, neutrophil-to-lymphocyte ratio (NLR) and white blood cell count (WBC) in 48 un-medicated MDD subjects (n = 17 with mild-to-moderate suicidal ideation [SI]) and 54 controls. IL-6 and TNF-α were combined into a composite inflammation score.There were no significant differences in 25(OH)D levels between MDD and controls (p = 0.24) or between MDD with and without SI (p = 0.61). However, 25(OH)D was negatively correlated with all measured inflammatory markers; these correlations were stronger in MDD subjects, and particularly in those with SI. MDD status significantly moderated the relationships between 25(OH)D and NLR (p = 0.03), and 25(OH)D and WBC (p 0.05), and SI significantly moderated the relationship between 25(OH)D and NLR (p = 0.03).The study was cross-sectional, thereby limiting causal inference, and had a small sample size. Only seventeen of the MDD subjects had SI.While 25(OH)D levels did not significantly differ in MDD vs. controls, or in MDD with or without SI, lower 25(OH)D was associated with indices of immune activation in MDD, especially in cases with SI. Although our findings do not address causality, they are consistent with findings that relatively low 25(OH)D levels in MDD are associated with a pro-inflammatory state.

While studies have speculated that immune function may play a role in how water, sanitation, hygiene, and nutritional (N+WSH) interventions may individually impact child growth and development, the combined effects of these interventions on immune system development are unknown. Here, we report on a trial in rural Bangladesh, where we cluster-randomized pregnant women into control and N+WSH arms. Among the birth cohort, we quantified plasma IL-1β, IL-6, TNF-α, IL-2, IL-12p70, IFN-γ, IL-4, IL-5, IL-13, IL-17A, IL-21, IL-10, and GM-CSF at ages 14 and 28 months. Cytokine ratios were included as prespecified outcomes to examine the net inflammatory environment. We assessed 704 children. After one year, TNF-α/IL-10, IL-12/IL-10, and IL-17A/IL-10 ratios were lower in the intervention group compared to the control group (mean difference: -0.12 to -0.19, p

Background:Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.Methods:We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.Results:In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.Conclusions:Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address ‘emergency states’ with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.Funding:Funded by the Bill and Melinda Gates Foundation.Clinical trial number:NCT01590095

Although several reports have documented heightened systemic inflammation in posttraumatic stress disorder (PTSD), few studies have assessed whether inflammatory markers serve as prospective biomarkers for PTSD risk. The present study aimed to characterize whether peripheral immune factors measured in blood samples collected in an emergency department immediately after trauma exposure would predict later chronic development of PTSD.Participants (N=505) were recruited from a hospital emergency department and underwent a 1.5-hour assessment. Blood samples were drawn, on average, about 3 hours after trauma exposure. Follow-up assessments were conducted 1, 3, 6, and 12 months after trauma exposure. Latent growth mixture modeling was used to identify classes of PTSD symptom trajectories.Three distinct classes of PTSD symptom trajectories were identified: chronic (N=28), resilient (N=160), and recovery (N=85). Multivariate analyses of covariance revealed a significant multivariate main effect of PTSD symptom trajectory class membership on proinflammatory cytokines. Univariate analyses showed a significant main effect of trajectory class membership on plasma concentrations of proinflammatory tumor necrosis factor α (TNFα) and interferon-γ (IFNγ). Concentrations of proinflammatory TNFα and IFNγ were significantly lower in individuals in the chronic PTSD class compared with those in the recovery and resilient classes. There were no significant differences in interleukin (IL) 1β and IL-6 concentrations by PTSD symptom trajectory class. Anti-inflammatory and other cytokines, as well as chemokines and growth factor concentrations, were not associated with development of chronic PTSD.Overall, the study findings suggest that assessing the proinflammatory immune response to trauma exposure immediately after trauma exposure, in the emergency department, may help identify individuals most at risk for developing chronic PTSD in the aftermath of trauma.

In this issue, David Jessop presents a commentary entitled The Power of Positive Stress and a Research Roadmap. I appreciate our Editor in Chief, James Herman’s invitation to provide a “commentary ...

Prior work has linked meditation practice to improvements in interference control. However, the mechanisms underlying these improvements are relatively unknown. In the context of meditation training, improvements in interference control could result either from increases in controlled attention to goal-relevant stimuli, or from reductions in automatic capture by goal-irrelevant stimuli. Moreover, few studies have linked training-related changes in attention to physiological processes, such as inflammatory activity, that are thought to influence cognitive function. This study addresses these gaps by examining associations between cognitive performance and cytokines in the context of an intensive meditation retreat. Participants were randomly assigned to complete 3 months of meditation training first, or to serve as waiting-list controls. The waitlist control participants then later completed a separate 3-month training intervention. We assessed participants’ interference control with a flanker task and used computational modeling to derive component processes of controlled and automatic attention. We also collected blood samples at the beginning, middle, and end of training to quantify changes in cytokine activity. Participants who completed training evidenced better controlled attention than waitlist controls during the first retreat intervention, and controls showed significant improvements in controlled attention when they completed their own, second retreat. Importantly, inflammatory activity was inversely associated with controlled attention during both interventions. Our results suggest that practice of concentration meditation influences interference control by enhancing controlled attention to goal-relevant task elements, and that inflammatory activity relates to individual differences in controlled attention.

Objective Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment “response” was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p < 0.001), TNF-α (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes (p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p = 0.019). Conclusion Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

Introduction Several lines of evidence indicate that increased inflammation is associated with Post-Traumatic Stress Disorder (PTSD). We have previously reported that peripheral inflammatory markers are significantly higher in combat-exposed veterans with than without PTSD. This study was designed to replicate these findings in a new study cohort using the same population and recruitment strategies. Methods Sixty-one male war veterans (31 PTSD and 30 control subjects) were included in this replication study. Levels of Interleukin-6, Tumor Necrosis Factor-alpha, Gamma interferon, and high-sensitivity C-reactive protein were quantified in blood samples. A standardized “total pro-inflammatory score” was calculated to limit the number of statistical comparisons. The Clinician Administered PTSD Scale (CAPS) rating scale was used to assess PTSD symptom severity. Results PTSD subjects had significantly higher total pro-inflammatory scores compared to non-PTSD subjects in unadjusted analysis (Cohen’s d = 0.75, p = 0.005) as well as after adjusting for potentially confounding effects of age, BMI, smoking, and potentially interfering medications and somatic co-morbidities (p = 0.023). There were no significant correlations between inflammatory markers and severity of symptoms within the PTSD group. Conclusions We replicated, in a new sample, our previous finding of increased inflammatory markers in combat-exposed PTSD subjects compared to combat-exposed non-PTSD controls. These findings strongly add to the growing literature suggesting that immune activation may be an important aspect of PTSD pathophysiology, although not directly correlated with current PTSD symptom levels in the PTSD group.

Racial discrimination has been linked to allostatic load (i.e., cumulative biological stress) among African American women. Coping is a central component of the stress response process. However, limited attention has been given to psychosocial processes involved in the stress response—critical for understanding biological pathways to health—in studies examining racial discrimination as a social determinant of health. We examined whether the superwoman schema (SWS), a multidimensional culture-specific framework characterizing psychosocial responses to stress among AA women, modifies the association between racial discrimination and allostatic load. We used purposive sampling to recruit a community sample of African American women ages 30–50 from five San Francisco Bay Area counties (n = 208). Path analysis was used to test for interactions while accounting for the covariance among SWS subscales using both linear and quadratic models. Significant interactions were observed between racial discrimination and four of the five SWS subscales. Feeling obligated to present an image of strength and an obligation to suppress emotions were each protective whereas feeling an intense motivation to succeed and feeling an obligation to help others exacerbated the health risk associated with experiencing racial discrimination. Our findings affirm the need to consider individual variability in coping and potentially other psychosocial processes involved in the stress response process; and offer several insights that may help elucidate the mechanisms by which racial discrimination gets “under the skin”.

Chronic psychological stress is associated with accelerated biological aging, immune dysfunction, and premature morbidity and mortality. Changes in the relative proportions of T cell subpopulations are thought to be a characteristic of immunological aging; however, understanding of whether these changes are associated with chronic psychological stress is incomplete. This study investigated associations between chronic caregiving stress and distributions of T cell phenotypes in a sample of high stress mothers of children with Autism Spectrum Disorder (caregivers; n = 91) and low stress mothers of neurotypical children (controls; n = 88). Immune markers assessed were naive (CD45RA + CD62L+), central memory (CD45RA-CD62L+), and effector memory (CD45RA-CD62L-) CD4+ and CD8+ T cells. We also examined the ratio of effector to naive (E:N) CD4+ and CD8+ T cells. In models adjusted for age, body mass index, race/ethnicity, and antidepressant use, caregivers displayed higher percentages of effector memory CD8+ and CD4+ T cells as well as lower percentages of naive CD8+ T cells and central memory CD8+ and CD4+ T cells compared to controls. Caregivers also displayed significantly higher E:N ratios for both CD4+ and CD8+ T cells. These findings were also independent of cytomegalovirus infection status. Furthermore, higher parental stress, across both groups, was related to several immune parameters. These findings provide preliminary evidence that chronic parental caregiving stress is associated with changes in relative proportions of T cell subpopulations that are consistent with accelerated immunological aging.

Summary Inflammation has been involved in the pathophysiology and treatment response of major depressive disorder (MDD). Plasma cytokine profiles of 171 treatment-naive MDD patients (none of the MDD patients received an adequate trial of antidepressants or evidence-based psychotherapy) and 64 healthy controls (HCs) were obtained. MDD patients exhibited elevated concentrations of 18 anti- and proinflammatory markers and decreased concentrations of 6 cytokines. Increased inflammasome protein expression was observed in MDD patients, indicative of an activated inflammatory response. The plasma of MDD patients was immunosuppressive on healthy donor peripheral blood mononuclear cells, inducing reduced activation of monocytes/dendritic cells and B cells and reduced T cell memory. Comparison between 33 non-responders and 71 responders at baseline and 12 weeks revealed that after treatment, anti-inflammatory cytokine levels increase in both groups, whereas 5 proinflammatory cytokine levels were stabilized in responders, but continued to increase in non-responders. MDD patients exhibit remodeling of their inflammatory landscape.

The range of psychosocial stress factors/processes (eg, chronic stress, distress states, coping, social adversity) were reviewed as they relate to immune variables in cancer along with studies of psychosocial interventions on these stress processes and immune measures in cancer populations. The review includes molecular, cellular, and clinical research specifically examining the effects of stress processes and stress-management interventions on immune variables (eg, cellular immune function, inflammation), which may or may not be changing directly in response to the cancer or its treatment. Basic psychoneuroimmunologic research on stress processes (using animal or cellular/tumor models) provides leads for investigating biobehavioral processes that may underlie the associations reported to date. The development of theoretically driven and empirically supported stress-management interventions may provide important adjuncts to clinical cancer care going forward.

Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.

Inflammation is reported in post-traumatic stress disorder (PTSD). Few studies have investigated circulating blood cells that may contribute to inflammation. We assessed circulating platelets, white blood cells (WBC) and red blood cells (RBC) in PTSD and assessed their relationship to inflammation and symptom severity. One-hundred and sixty-three male combat-exposed veterans (82 PTSD, 81 non-PTSD) had blood assessed for platelets, WBC, and RBC. Data were correlated with symptom severity and inflammation. All cell counts were significantly elevated in PTSD. There were small mediation effects of BMI and smoking on these relationships. After adjusting for these, the differences in WBC and RBC remained significant, while platelet count was at trend level. In all subjects, all of the cell counts correlated significantly with inflammation. Platelet count correlated with inflammation only in the PTSD subjects. Platelet count, but none of the other cell counts, was directly correlated with PTSD severity ratings in the PTSD group. Combat PTSD is associated with elevations in RBC, WBC, and platelets. Dysregulation of all three major lineages of hematopoietic cells in PTSD, as well as their significant correlation with inflammation, suggest clinical significance of these changes.

Posttraumatic stress disorder (PTSD) is associated with increased risk for Type 2 diabetes and cardiovascular disease (cardiometabolic disease), warranting research into targeted prevention strategies. In the present case–control study of 160 young (mean age 32.7 years) male military veterans, we aimed to assess whether PTSD status predicted increased markers of cardiometabolic risk in otherwise healthy individuals, and further, to explore biological pathways between PTSD and these increased markers of cardiometabolic risk. Toward these aims, we compared measures of cardiometabolic risk, namely insulin resistance (IR) (HOMA-IR), metabolic syndrome (MetS) and prediabetes, between 80 PTSD cases and 80 controls without PTSD. We then determined whether PTSD-associated increases in HOMA-IR were correlated with select biological variables from pathways previously hypothesized to link PTSD with cardiometabolic risk, including systemic inflammation (increased C-reactive protein, interleukin-6, and tumor necrosis factor α), sympathetic over-activity (increased resting heart rate), and neuroendocrine dysregulation (increased plasma cortisol or serum brain-derived neurotrophic factor (BDNF)). We found PTSD diagnosis was associated with substantially higher HOMA-IR (cases 4.3 ± 4.3 vs controls 2.4 ± 2.0; p 0.05). Cases also had increased pro-inflammatory cytokines (p

Poor breast cancer–related quality of life is associated with flattened cortisol rhythms and inflammation in breast cancer survivors and women with advanced disease. We explored the associations of cancer-specific distress (Impact of Events Scale), mood (Profile of Mood States), activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient) and cortisol (diurnal slope) circadian rhythms, and inflammation (interleukin-6) with quality of life (Functional Assessment of Cancer Therapy–Breast) among patients awaiting breast cancer surgery ( N = 57). Models were adjusted for differences in age and cancer stage. Distress and mood disturbance were significantly correlated with lower quality of life. Ethnic differences in the relationship between distress and mood disturbance with global quality of life and subscales of quality of life were observed. Actigraphic measures showed that in comparison with non-Hispanic patients, African Americans had significantly poorer activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient). Circadian disruption and inflammation were not associated with quality of life. Physiological dysregulation and associated comorbidities may take time to develop over the course of disease and treatment.

While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p

Sense of coherence (SOC) reflects the degree to which an individual perceives their world as comprehensible, manageable, and meaningful. Among cancer populations, SOC has been linked with greater quality of life and reduced mortality, suggesting that SOC may serve as a marker of resilience in the context of chronic disease. Utilizing a published adaptation of the transactional model of stress and coping, we hypothesized greater SOC would be associated with adaptive coping, more regulated cytokine response, and lower fatigue. Sixty-two lung cancer patients provided self-report data on SOC, coping, and fatigue. PBMC were incubated with stimulators of acquired and innate immunity (PHA, LPS), and cytokines were measured (pro-inflammatory: IL-1beta IL-6, TNF-alpha; Type 1/TH1: IFN-gamma; Type 2/TH2: IL-5). Linear regressions tested hypotheses. Greater SOC was associated with emotionally expressive coping (p = 0.005), an attenuated IL-5 response to PHA (p = 0.038) and IFN-gamma response to LPS (p=.001); and lower fatigue (p

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.