Jacqueline A. Bartlett

HIV-relevant sexual behavior among a healthy inner-city heterosexual adolescent population in an endemic area of HIV

The AIDS crisis has devastated segments of the population including the gay community and those who use intravenous drugs. HIV has spread to other groups including prostitutes and those with other sexually transmitted diseases. We have been studying adolescents in a major Northeast city where there is a major HIV/AIDS epidemic. Despite high levels of AIDS related knowledge, these adolescents reported high levels of sex risk behaviors. In addition, our data suggests that even moderate alcohol or marijuana use predicts high risk sexual behaviors. These data indicate the urgent need to develop prevention strategies for the spread of HIV among inner-city youth based upon relevant predictors of risk behaviors. The coupling of HIV in inner-city populations with a high frequency of risk behaviors in adolescents demands an immediate public health response.

Depression and immunity: clinical factors and therapeutic course ☆

While many reports describe associations between depressive disorders and altered immunity, findings have not been fully consistent. Diagnostic subtype, demographic factors such as age and gender, medical characteristics, and the immune measures selected for assessment may have contributed to the heterogeneous findings. In a study of 21 medically healthy young adults with major depression, we found, consistent with previous reports, evidence of increased lymphocyte activation to mitogen challenge and decreased natural killer (NK) cell numbers and function during acute depression. Fifteen subjects were followed longitudinally. T, CD4+, CD29+, and CD45RA+ lymphocytes and T-cell mitogen responses decreased significantly (P<0.05) during 6 weeks of pharmacotherapy and concurrent clinical improvement. There was no change in NK activity or CD56+ cells. The longitudinal effects appeared unrelated to tricyclic antidepressant levels. Changes in the immune system with short-term clinical improvement in depressed patients are not uniform providing further evidence that several mechanisms are involved in the altered immunity associated with clinical depression.

Influence of Neurological Level on Immune Function Following Spinal Cord Injury: A Review

Abstract Due to the high incidence of lifelong infections in persons with spinal cord injury (SCI), the authors examined level of injury-relateifimmune characteristics in a cohort of subjects with chronic SCI. Since the sympathetic nervous system and the endocrine system are known to be modulators of immune function, one possible explanation for heightened incidence of infections includes dysregulation of sympathetic outflow tracts in individuals with tetraplegia or high paraplegia. Natural killer cell cytotoxicity (NKCC) and bactericidal function of circulating neutrophils were assayed in a group of 10 individuals with chronic complete cervical SCI, a group of 8 individuals with paraplegia with injuries below the main sympathetic outflow (T-1 0 and below) and a group of 18 age- and sex-matched controls. In addition, a psychiatric assessment of depression was performed as well as assays of pituitary and adrenal functions. Analyses revealed no significant differences in immune function between all subjects with SCI combined and their matched controls. Further analyses stratifying based on presence or absence of sympathetic dysregulation revealed significantly impaired phagocytic ability and a trend toward reduced NKCC in the group with tetraplegia compared with their controls. Hormonal assays showed that dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DS) were higher in individuals with tetraplegia than controls, but no such differences were observed in individuals with paraplegia compared with their controls. The results of this study suggest that individuals sustaining complete cervical SCI experience alterations in immune function, while those with lesions at or below T-10 do not. These findings of level of injury related immune alteration could not be explained by mood differences. This paper is a review of previously published work and the authorsș current thinking regarding increased acquisition of infections in this population.

Impaired phagocytosis of Staphylococcus aureus in complete tetraplegics

Accumulating evidence implicates the sympathetic nervous system as a modulator of immune function. Immune alteration has been observed in survivors of cervical level spinal cord injury, possibly because of dysregulation of the sympathetic outflow tracts. The majority of immune studies in the spinal cord-injured population have focused on lymphocytes. Because of the high incidence of infections in this population, we hypothesized that the immune alteration would extend to the cells of the myeloid lineage. This hypothesis was tested by analyzing the phagocytic and bactericidal function of circulating neutrophils in response to Staphylococcus aureus. A group of ten individuals with complete cervical spinal cord injury, a group of eight paraplegics with injuries below the majority of sympathetic outflow (T-10 and below), and age- and gender-matched controls for each subject were studied. In addition, a psychiatric screening for depression was completed by all subjects and controls. Paired t test revealed significantly impaired phagocytic ability in the tetraplegic group compared with their controls. The paraplegic group did not demonstrate these findings. Our results suggest that individuals who have sustained complete cervical spinal cord injury have alteration in immune function compared with neurologically intact controls, whereas those with lesions at or below T-10 do not. This in vitro finding may be related to infection after cervical spinal cord injury. The mechanism may involve dysregulation of the sympathetic arm of the autonomic nervous system.

Altered innate immunity following spinal cord injury

Study Design:Cross-sectional, paired cohort study.Objectives:To replicate the finding of impaired immunocyte function following spinal cord injury (SCI). To determine whether cellular immune function in SCI subjects with decentralized sympathetic nervous system (SNS) (T6 and above) varies from SCI subjects with intact SNS (below T6).Setting:University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, NJ, USA.Method:In vitro immune assays: (1) natural killer (NK) cell cytotoxicity using a K562 target cell line in a 4-h chromium51 release assay. The mean of three samples for each effector-to-target (E:F) ratio (25:1, 50:1, 100:1) was used in the analyses. (2) Cell enumeration was performed using commercially available antibodies and standard flow cytometry techniques.Results:Participation of 36 SCI subjects and 36 individually age- and sex-matched healthy controls. SCI subjects were stratified into two groups, that is, neurologic level of injury (NLI) at T6 or above (26 subjects) and NLI below T6 (10 subjects). No statistically significant differences were identified between NLI T6 and above and NLI below T6 groups for the NK cytotoxicity assay. There was a statistically significant reduction in NK cell numbers in all subjects with SCI as compared to their paired controls. There was a statistically significant reduction in NK cell cytotoxicity in SCI subjects, relative to the controls for E:F ratio of 100:1 (F=6.18, d.f.=34, P=0.02).Conclusion:We replicated the finding of decreased NK cell number and cytotoxicity in SCI subjects. The mechanism behind these findings needs to be further investigated, with the long-term goal of developing therapeutic strategies to improve immune function.

Adrenal and pituitary hormone patterns after spinal cord injury.

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. We hypothesized that immune alterations, which were related to the level of injury, found in a cohort of spinal cord-injured subjects may be influenced by altered hormonal patterns postinjury. Therefore, we investigated aspects of both pituitary and adrenal function in the same cohort of spinal cord-injured subjects. We found significant elevations in both cortisol and dehydroepiandrosterone sulfate in chronic spinal cord-injured survivors compared with their able-bodied age- and gender-matched controls. Levels of dehydroepiandrosterone, adrenocorticotropin, and prolactin were not different in spinal cord-injured subjects overall compared with their controls. Both dehydroepiandrosterone sulfate and dehydroepiandrosterone were higher in tetraplegics compared with their controls, but we found no such differences in paraplegics compared with their controls. When the two groups of spinal cord-injured subjects were compared with each other, we also found differences between these two subject groups in dehydroepiandrosterone sulfate and dehydroepiandrosterone (higher in the tetraplegics compared with paraplegics). We found no differences between either group of spinal cord-injured subjects and their controls for adrenocorticotropin, prolactin, or cortisol. These data suggest that some hormonal differences between subjects and their controls may be further related to the level of injury (specifically dehydroepiandrosterone and dehydroepiandrosterone). Finally, we investigated correlations within subjects for the above hormones. Dehydroepiandrosterone sulfate and prolactin were highly correlated (the higher the dehydroepiandrosterone sulfate, the higher the prolactin) but only in the tetraplegic subjects.

Immunity in adolescents with major depression.

OBJECTIVE The association between major depression (MD) and altered immunity appears to be age-related, with differing immune changes found in prepubertal children, young adults, and older adults. There is limited information concerning immunity in adolescents with MD. METHOD Thirty-six otherwise healthy medication-free adolescents (aged 14-20; 23 female) from a community sample, meeting Diagnostic Interview Schedule for Children DSM-III-R criteria for unipolar MD, were compared with 36 nondepressed adolescents matched by gender, age, and racial background. A battery of quantitative and functional immune measures was obtained. RESULTS MD adolescents had increased (p < .05) circulating lymphocytes and lymphocyte subsets; however, altered distribution of lymphocyte subsets was found only for activated T (HLA-DR+) cells (p < .004) and, possibly, natural killer (NK) (CD56+) cells (p < .06), each showing lower percentages in the MD adolescents. Concanavalin A (but not phytohemagglutinin or pokeweed mitogen) mitogen response was lower in the MD adolescents (p < .02). NK cell activity was elevated at higher effector-target ratios (p < .001), an effect not associated with the number of circulating CD56+ (NK) cells. CONCLUSIONS Depressed adolescents showed changes in immune measures that have been found to be altered in other MD groups, although the pattern of effects differs.

Panic disorder and immunity: few effects on circulating lymphocytes, mitogen response, and NK cell activity.

Altered immune measures are commonly found in major depression (MD), however, less is known about the immune system in anxiety disorders. We examined quantitative and functional in vitro immune measures in patients with panic disorder (PD), which is often comorbid with MD. Fourteen otherwise healthy medication-free adults (ages 23-49; 11 female) meeting SCID-UP DSM-IIIR criteria for PD with agoraphobia and without current MD, were compared with 14 subjects free of PD, MD, or other major psychiatric disorders, matched by gender, age, and racial background. PD was associated with decreased percentage (p<.03) and total (p<.03) circulating CD19+ B lymphocytes, but no differences in other enumerative lymphocyte measures. Mitogen responses (Con A, PHA, PWM) did not differ except for possibly decreased PHA in PD (p<.06). NK cell activity did not differ between PD and control subjects. The few immune measure changes in PD contrast with those found in MD, providing further evidence for the specificity of immune changes in psychiatric disorders.

Immune Function in Healthy Inner-City Children

ABSTRACT The importance of investigating immunity in healthy children has been underscored in the last few years by studies of the immune pathology of childhood illnesses, including human immunodeficiency virus. This study reports both ennumerative and functional immune measures in healthy inner city children. A total of 152 of 207 children studied were completely heathy at the time of venipuncture and were included in this study. Laboratory immune batteries were completed (or begun) the same day as venipuncture. Relationships between age, gender, ethnicity, and immunity were then analyzed. We found that gender predicted both the absolute number and the percentage of T cells and helper cells and the percentage of natural killer cells. Total leukocyte counts and percentages of lymphocytes and granulocytes were related to ethnicity, as was the response to mitogen stimulation (concanavalin A and pokeweed mitogen) and phagocytic ability. In conclusion, age, gender, and ethnicity factors were found to contribute to differences in various immune measures in children and require further investigation.

Stress, Immunity, and Health

Publisher Summary This chapter describes the stress-immunity-health model that is implicit in most psychoneuroimmunology (PNI) research; it focuses on definitional issues surrounding the models various components. It reviews the research on humans that examines the complete model, and to provide a conceptual and methodological context within which to evaluate those studies. The chapter focuses on research that contains some measure of “stress” within the psychosocial component of the model. It reviews the evidence that supports the shorter links in the model: connecting stress to immune function, and immune function to health outcomes. It discusses the role of mediating mechanisms, behavioral and neuroendocrine. The concern for methodological rigor takes on greater importance in PNI because new paradigms that do not appear to be consistent with current scientific thinking are subject to skepticism and disbelief. The fact that PNI continues to be the target of skepticism, is attested to by the controversy generated by a study of the impact of psychosocial factors on clinical outcome in advanced cancer patients.