In this review, the authors examine the evidence linking social support to physiological processes and characterize the potential mechanisms responsible for these covariations. A review of 81 studies revealed that social support was reliably related to beneficial effects on aspects of the cardiovascular, endocrine, and immune systems. An analysis of potential mechanisms underlying these associations revealed that (a) potential health-related behaviors do not appear to be responsible for these associations; (b) stress-buffering effects operate in some studies; (c) familial sources of support may be important; and (d) emotional support appears to be at least 1 important dimension of social support. Recommendations and directions for future research include the importance of conceptualizing social support as a multidimensional construct, examination of potential mechanisms across levels of analyses, and attention to the physiological process of interest.

The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health.

An accumulation of data has been obtained showing hormones from neuroendocrine tissues influence various parameters of lymphocytes' biological activities and, in a reciprocal fashion, products of the immune system have been shown to influence neuroendocrine function. These findings have led to the formation of a new scientific subdiscipline which we term neuroimmunoendocrinology. The implication of these studies is that under various cognitive stimuli, hormones produced by the neuroendocrine system may influence the immune system in its response to internal (network hypothesis) and external stimuli (virus, tumors, bacteria, etc.). A converse situation may arise in that under noncognitive stimulations such as disease or infection, the immune system may operate in eliminating the infectious agent as well as producing hormones (i.e., adrenocorticotropin hormone and/or endorphins), lymphokines, and monokines, which may influence many physiologic responses. Moreover, the findings that hormone receptors are common to both systems provide additional evidence that the immune system has the capacity to react on a molecular level much like a circulating neuron or specialized endocrine cell. In this summary, we will describe the interrelatedness between the immune and neuroendocrine systems with regard to (1) the effect of lymphokines and monokines on neuroendocrine tissue, (2) the production of neuroendocrine hormones by cells of the immune system, (3) the influence of such hormones on immunocyte function as measured by in vitro biological assays, (4) the biochemical evidence for shared receptors on cells of the immune and neuroendocrine systems, and lastly (5) some of the clinical implications.

A molecular basis for bidirectional communication between the immune and neuroendocrine systems.

The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+) Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively Concentrations of IL-6 and cortisol were assessed in plasma Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations Effects of sleep were not mediated by changes in cortisol The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge

Effects of sleep and circadian rhythm on human circulating immune cells

This article provides a review of empirical evidence linking emotional processes to immune function in humans. Acute stressors have produced mixed effects on immunity, presumably through differential activation of physiological stress systems. Chronic stress has been associated with suppression of immune function, and there is evidence that the immune system may not adapt over time. Effects of stress accompanying social disruption and psychological depression, when demonstrated, have been consistently adverse. Certain personality styles may enhance or degrade immune response. Relationships between psychosocial factors and immunity have been identified for several diseases, including cancer, acquired immune deficiency syndrome, and autoimmune diseases; psychosocial interventions have been tested with variable results. Theoretical and methodological considerations are summarized and directions for future research suggested.

Stress, emotion, and human immune function.

Stress and immunity: an integrated view of relationships between the brain and the immune system.

We have previously demonstrated that mitogen responsiveness of mononuclear cells (MNC) from peripheral blood is reduced after a single injection of epinephrine to human subjects. The purpose of the present study was to characterize the relative distributions of MNC subsets after epinephrine administration using monoclonal antibodies and conventional cell markers. The absolute number of circulating MNC increased 64% within 30 min after injection of epinephrine, and returned to baseline by 2 hr. Analysis of MNC subsets revealed that there were no changes in the relative percentages of total T lymphocytes [T3+ cells, or neuraminidase-treated sheep red blood cell rosettes (EN-rosettes)], B lymphocytes (B1+, or cells with surface-bound immunoglobulin), or monocytes (by morphologic criteria) after epinephrine administration. The percentage of inducer T cells (T4+) declined at 30 and 60 min postinjection. Overall, the percentage of suppressor/cytotoxic T cells (T8+) did not change after injection of epinephrine; however, analysis of individual subjects revealed opposing responses of this subset. The T4:T8 ratio was 2.19 before injection, declined to 1.56 at 60 min, then increased to 3.10 2 hr postinjection. The percentage of natural killer/killer cells (HNK-1+) increased from a baseline of 15.5% before epinephrine injection to 29.6% at 30 min postinjection, then declined to 11.4% at 2 hr. Therefore, the administration of physiologic doses of epinephrine results in changes in the relative proportions of lymphocyte subsets in peripheral blood, in addition to reduced mitogen responsiveness as reported previously.

Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans.

A single subcutaneous injection of 0.2 mg epinephrine into healthy human subjects caused a transient lymphocytosis in peripheral blood. Mononuclear cells (MNC), isolated at various times after epinephrine administration, were cultured in the presence of mitogens. The blastogenic responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were significantly reduced for up to 60 min post-epinephrine (p less than 0.05); the response to concanavalin A (Con A) was reduced in the 15-min samples only. All responses returned to pre-injection levels by 120 min post-injection. Removal of adherent monocytes from MNC isolates before culture did not restore normal mitogen responsiveness. When MNC were cultured in the absence of mitogens, there was no difference in survival between pre- and post-epinephrine samples. Incubation of untreated MNC for 2 hr or 18 hr in vitro with various concentrations of epinephrine (10(-5) to 10(-1) mg/ml) had no effect upon the subsequent blastogenic response to mitogens. Other workers have reported that epinephrine administration causes alterations in the composition of the circulating lymphocyte pool. Taken together, these data suggest that the reduction in mitogen responsiveness after epinephrine is the result of changes in the distribution of lymphocyte subclasses in peripheral blood.

Decrease in mitogen responsiveness of mononuclear cells from peripheral blood after epinephrine administration in humans.

INTRODUCTION
PTSD is common among veteran combatants. PTSD is characterized by brain changes, for which available treatments have shown limited effect. In a short-term study, we showed that hyperbaric oxygen therapy (HBOT) induced neuroplasticity and improved clinical symptoms of veterans with treatment-resistant PTSD. Here, we evaluated the long-term clinical symptoms of the participants of that study.


MATERIALS AND METHODS
Veterans from our short-term study were recruited 1 or more years after completing HBOT. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and self-reported questionnaires were administered at a single site visit. Changes in clinical scores between long-term, short-term, and pretreatment evaluations were analyzed.


RESULTS
Of the 28 participants who received HBOT during or following the short-term study, 22 agreed to participate in the current study. At a mean of 704 ± 230 days after completing the HBOT course, the mean CAPS-5 score (26.6 ± 14.4) was significantly better (lower) than at the pre-HBOT evaluation (47.5 ± 13.1, P < .001) and not statistically different from the short-term evaluation (28.6 ± 16.7, P = .745). However, for the CAPS-5 subcategory D (cognition and mood symptoms), the mean score was significantly better (lower) at long-term than at short-term evaluation (7.6 ± 5.1 vs. 10.0 ± 6.0, P < .001). At the long-term compared to the pretreatment evaluation, higher proportions of the participants were living with life partners (10 (46%) vs. 17 (77%), P = .011) and were working (9 (41%) vs. 16 (73%), P = .033). Decreases were observed between pretreatment and the long-term follow-up, in the number of benzodiazepine users (from 10 (46%) to 4 (18%), P = .07) and in the median (range) cannabis daily dose (from 40.0 g (0-50) to 22.5 g (0-30), P = .046).


CONCLUSIONS
The beneficial clinical effects of HBOT are persistent and were not attenuated at long-term follow-up of about 2 years after completion of HBOT. Additional long-term effects of the treatment were observed in social function and in decreased medication use.

https://academic.oup.com/milmed/advance-article-pdf/doi/10.1093/milmed/usac360/47307485/usac360.pdf

I Kutz

Papers

Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans.

Decrease in mitogen responsiveness of mononuclear cells from peripheral blood after epinephrine administration in humans.

Hyperbaric Oxygen Therapy for Veterans With Treatment-resistant PTSD: A Longitudinal Follow-up Study.