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Nurses play a major role in the health care delivery system; therefore, education of nurses is critical to successful prevention programs for persons with HIV. Little is known about nurses' knowledge of HIV in India. The purpose of this study was to determine the effects of a nurse-led train-the-trainer HIV education program on improving the HIV knowledge of nurses. A group of senior nurses (N = 10), were responsible for training a cohort of 10 nurses each, totaling 100 nurses. The 2-day training program included HIV epidemiology and etiology, infection control, psychosocial support, counseling, modes of transmission, natural history of the disease, symptoms of early and late disease, diagnostic testing, and legal and ethical issues. Pre- and posttest scores were calculated using a self-administered structured questionnaire that measured HIV-related knowledge in terms of cognitive and transmission knowledge. Paired t-tests indicated that both measures of HIV knowledge improved significantly from pretest to posttest. [ABSTRACT FROM AUTHOR]

Approximately 30% of women successfully treated for breast cancer suffer persistent fatigue of unknown origin. Recent studies linking inflammatory processes to central nervous system-mediated fatigue led us to examine cellular immune system status in 20 fatigued breast cancer survivors and 19 matched non-fatigued breast cancer survivors. Fatigued survivors, compared with non-fatigued survivors, had statistically significantly increased numbers of circulating T lymphocytes (mean 31% increase, 95% confidence interval [CI] = 6% to 56%; P =.015 by two-sided analysis of variance [ANOVA]), with pronounced elevation in the numbers of CD4+ T lymphocytes (mean 41% increase, 95% CI = 15% to 68%; P =.003 by two-sided ANOVA) and CD56+ effector T lymphocytes (mean 52% increase, 95% CI = 4% to 99%; P =.027 by two-sided ANOVA). These changes were independent of patient demographic and treatment characteristics. Absolute numbers of B cells, natural killer cells, granulocytes, and monocytes were not altered. The increased numbers of circulating T cells correlated with elevations in the level of serum interleukin 1 receptor antagonist (for CD3+ cells, r =.56 and P =.001; for CD3+/CD4+ cells, r =.68 and P<.001, by Spearman rank correlation). Results of this study suggest that persistent fatigue in breast cancer survivors might be associated with a chronic inflammatory process involving the T-cell compartment. These results require confirmation in a larger study that is specifically designed to address this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Aging is associated with decline in both cell-mediated and humoral immunity and may contribute to increased incidence and severity of infections in frail elderly. Exercise, depending on intensity, has significant effects on the immune system. We conducted a randomized, controlled clinical trial of a 32-week functionally oriented exercise program in frail elderly living in nursing homes and determined whether the exercise intervention was associated with a change in immune parameters in this frail elderly nursing home population.Methods: Nursing home residents were randomly assigned to an intervention (n = 94) and control group (n = 96). The intervention consisted of a functionally oriented endurance and resistance exercise training that was provided every 2 hours from 8:00 AM to 4:00 PM for 5 days a week for 8 months. Lymphocyte subpopulations, including activation markers (CD28, CD25, HLA-DR), in vitro proliferation, and soluble products of cytokine activity (neopterin and sTNF-RII) in serum were measured by taking blood samples at baseline and after 8 weeks and 32 weeks of the intervention.Results: Exercise training did not induce changes in lymphocyte subpopulations, activation markers (CD28, CD25, HLA-DR), in vitro proliferation, and soluble products of cytokine activity (neopterin and sTNF-RII) in serum.Conclusions: A 32-week exercise intervention did not bring about beneficial or detrimental effects on immune parameters in the frail elderly nursing home population and may explain why the intervention was not associated with a change in the incidence of infections in the intervention group compared with the control group. [ABSTRACT FROM AUTHOR]

Investigates the cardiovascular and cellular immune system responses of healthy young men during brief mental arithmetic stress. Effects of the opiate antagonist naloxone on measures of cellular immune system responses during rest and brief psychological stress; Role of endogenous opioidsin mediating immunological change to stress; Increase in natural killer cell activity during mental arithmetic.

Objective. The increased use of antiretroviral therapy (ART) has reduced the morbidity and mortality associated with HIV, adversely leading to the emergence of HIV drug resistance (HIVDR). In this study we aim to evaluate the prevalence of HIVDR mutations in ART-naive HIV-1 infected patients from northern India. Design. Analysis was performed using Viroseq genotyping system based on sequencing of entire protease and two-thirds of the Reverse Transcriptase (RT) region of pol gene. Results. Seventy three chronic HIV-1 infected ART naïve patients eligible for first line ART were enrolled from April 2006 to August 2008. In 68 patients DNA was successfully amplified and sequencing was done. 97% of HIV-1 strains belonged to subtype C, and one each to subtype A1 and subtype B. The overall prevalence of primary DRMs was 2.9% [2/68, 95% confidence interval (CI), 0.3%-10.2%]. One patient had a major RT mutation M184V, known to confer resistance to lamivudine, and another had a major protease inhibitor (PI) mutation D30N that imparts resistance to nelfinavir. Conclusion. Our study shows that primary HIVDR mutations have a prevalence of 2.9% among ART-naive chronic HIV-1 infected individuals.

Background: Clinicians and associated health professionals charged with prescribing antiretroviral therapy (ART) deal with continuously evolving new drugs and combinations. To meet the needs of clinicians in India for ongoing education in this field, continuing medical education (CME) programmes on ART for HIV/AIDS were developed, conducted, evaluated and revised. Over a 2-year period, 2005-2007, 3 CME programmes for ART were conducted for physicians and a fourth (predominantly) for paediatricians., Methods: Both 1- and 2-day CME programmes on various aspects of ART were held on weekends for professionals treating patients with AIDS in Delhi and adjacent states. Topics included characteristics of ART drugs, their dosages, monitoring and toxicity management, adherence, complications of therapy, dealing with treatment failure and HIV co-infections. These topics were addressed in lectures and group discussions and via case presentations. Programmes were evaluated by anonymous response to questionnaires, by a 1-year follow up of participants and by informal discussions with participants and faculty. Detailed analyses and a recommended format for these programmes are presented., Results: The CMEs were attended primarily by clinicians (physicians and paediatricians). Nurses, laboratory scientists, and others involved in the treatment of AIDS also attended the programmes. An interactive workshop format was evolved with substantial time devoted to discussions and case analyses. One-day programmes such as the one included here can be comprehensive and effective. The educational needs of healthcare professionals who provide care and support to patients receiving ART were similar to those of the prescribing doctors. Because of new drugs being made available and with continued clinical experience, updated programme content was required each year. Participants preferred case-based interactive discussions rather than didactic lectures. Participants suggested that there should be more time for discussion after each talk., Conclusion: Annual CME programmes focused on ART are required to meet the professional needs of clinicians in India for providing quality care management to patients with AIDS.

This study is designed to assess AIDS knowledge among Homeopathy educators and physicians in India, which has not been evaluated previously. India now has the largest number of HIV infected persons worldwide, with an estimated cumulative 5.1 million infections. Homeopathy is the dominant system among the nationally-recognized alternative or complementary systems of medicine, which collectively provide health care to around 600 million people in India. Homeopathy, with its holistic and patient-centered approach, has a wide reach to people at risk of contracting human immunodeficiency virus (HIV). Participants were 68 homeopathy physicians (34 educators and 34 practitioners) who completed a CDC questionnaire measuring HIV/AIDS Knowledge regarding AIDS. This study reports the current level of knowledge of, and attitudes about, HIV/AIDS among homeopathy educators and practitioners. These findings will assist in the development of an education module to equip homeopathic health care personnel to impart accurate AIDS information and prevention counseling to their patients in an efficient manner.

Focus group discussions were conducted to assess factors that might impact participation of subgroups in Chennai for future HIV vaccine trials. The participants were 112 men and women representing the following: (1) transport workers; (2) clients who attended a sexually transmitted disease clinic; (3) injection drug users; (4) men having sex with men; (5) women in sex work; and (6) monogamous married women. Participants expressed an intense interest in future HIV vaccine trials. Willingness to participate in future trials included altruism and the desire to have a protective vaccine for the future. Assurances regarding stigma and confidentiality, and compensation for families in the event of a poor outcome with a future HIV vaccine trial were reported. Concerns also centered on the impact of seroconverting, and a possible increase in risk behaviors. The need for education and counseling about the dangers of engaging in risky behavior during and after participating in a future HIV vaccine trial is discussed.

Background & Objectives: In India, phase-I human clinical trials for a preventive HIV vaccine are being conducted at Pune and Chennai Centres. In order to find out the willingness of populations at risk to participate in future preventive HIV vaccine trials (HIVVTs) and to assess the factors that enhance or deter them from participation, a study was conducted at Chennai and Madurai in Tamil Nadu., Methods: This cross-sectional study was conducted among transport workers, people attending sexually transmitted infection clinics, injection drug users, men having sex with men, women in sex industry and a representative sample of monogamous married women, by employing measurement scales. A structured questionnaire on knowledge and attitudes about the HIV vaccine was used to measure the participants' knowledge and attitudes about HIV vaccine and HIVVTs., Results: Of the 112 participants, 67 (60%) were men. Mean age of the respondents was 32 yr; 68 per cent were high school educated. Majority of respondents were willing to participate in a future HIVVT and the reasons were altruism, protection from HIV, and support for the researchers. Major concerns were vaccine efficacy, side effects of the vaccine and the impact of a HIV vaccine on the participants' lives. Majority (85%) agreed that sex without condom would not be safe despite the availability of an HIV vaccine., Interpretation & Conclusion: It is likely that high-risk volunteers will be willing to enroll in HIVVTs. Barriers and concerns should be dealt with carefully by providing correct information. Also there is a need for more education to ensure participants' understanding of key concepts of HIV vaccine trial.

This study investigated circulating natural killer (NK), CD4+ and CD8+ cells in response to acute psychological challenge among mothers of child cancer survivors with and without posttraumatic stress symptoms (PTSS). Control mothers of healthy children (n=9) were compared to 17 cancer mothers with (PTSS: n=9) and without PTSS (No PTSS: n=7) under conditions of rest, after a generic stressor (MAT: mental arithmetic task) and a personalized stressor (script-driven trauma imagery), and after recovery from each stressor. Results indicate the PTSS group had higher percentage CD4+ and lower CD8+ levels than non-symptomatic women and blunted NK reactivity to generic challenge. Multiple regression analyses indicated PTSS effects were independent of self-reported distress. Contrary to expectations, cancer mothers without PTSS were not significantly different from controls on tonic or phasic immune outcomes. Also unlike predictions, reactivity to challenge was greatest to the non-social MAT stressor compared to the personalized challenge for all groups. Conclusions are constrained by study limitations (e.g., small sample size and potential phase order effects). Nonetheless, results are consistent with an emerging literature on PTSS-associated immune differences and further suggest these effects may be distinct from that associated with subjective distress more generally.

Background: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation., Methods: This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models., Results: The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P=.0009), endogenous interferon (P=.00039) and interleukin-6 (P=.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4+ cell count (P=.0165) and HIV-1 RNA level (P=.1220), we found that elevated values for neopterin (P=.0002) and, to a lesser extent, endogenous interferon (P=.0053) were the strongest predictors of increased risk of clinical disease progression 6 months later., Conclusions: Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an inexpensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings.

Approximately 30% of breast cancer survivors report persistent fatigue of unknown origin. We have previously shown that cancer-related fatigue is associated with alterations in immunological parameters and serum cortisol levels in breast cancer survivors. The current study examined the diurnal rhythm of salivary cortisol in fatigued and non-fatigued breast cancer survivors. Salivary cortisol measures were obtained from breast cancer survivors with persistent fatigue (n=13) and a control group of non-fatigued survivors (n=16). Participants collected saliva samples upon awakening and at 1200, 1700, and 2200 h on two consecutive days. Diurnal cortisol slope for each day was determined by linear regression of log-transformed cortisol values on collection time and analyzed using multi-level modeling. Fatigued breast cancer survivors had a significantly flatter cortisol slope than non-fatigued survivors, with a less rapid decline in cortisol levels in the evening hours. At the individual patient level, survivors who reported the highest levels of fatigue also had the flattest cortisol slopes. Group differences remained significant in analyses controlling for demographic and medical factors, daily health behaviors, and other potential confounds (e.g. depressed mood, body mass index). Results suggest a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in breast cancer survivors with persistent fatigue.

Background: Epidemiologic studies have identified psychological risk factors for specific physical diseases, but the biological mechanisms mediating these relationships remain poorly defined., Methods: Social inhibition and autonomic nervous system (ANS) activity were assessed on multiple occasions in 54 gay men with asymptomatic human immunodeficiency virus (HIV) infection. Following baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were monitored for 12-18 months to assess relationships between ANS activity and HIV pathogenesis., Results: We confirmed the previously reported relationship between socially inhibited temperament and vulnerability to viral pathology. Plasma viral load set-point was elevated eight-fold in socially inhibited individuals, and these individuals showed poorer virologic and immunologic response to initiation of highly active antiretroviral therapy (HAART). Effects were independent of duration of infection, HAART regimen, demographic characteristics, and health-relevant behavior. Neurophysiologic assessments documented elevated ANS activity in socially inhibited individuals, and mediational analyses showed that such differences could account for 64%-92% of the covariance between social inhibition and virologic parameters., Conclusions: These data provide the first clinical evidence that differential neural activity mediates relationships between psychological risk factors and infectious disease pathogenesis. Such findings also suggest novel targets for adjunctive therapy in long-term control of HIV-1 disease.

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 microg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4 degrees C for short periods of time or at -70 degrees C for longer periods and tested within the same run to minimize interassay variability.

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.

This study tested the hypothesis that cognitive processing about a past bereavement would produce increases in goals and priorities indicative of finding positive meaning from the loss. It was further hypothesized that increases in meaning-related goals would be associated with changes in immune function, specifically increased natural killer cell cytotoxicity (NKCC). Cognitive processing was manipulated using written emotional disclosure. Forty-three women who had lost a close relative to breast cancer wrote about the death (cognitive processing/disclosure group) or about nonemotional topics weekly for 4 weeks. Contrary to predictions, written disclosure did not induce changes in meaning-related goals or NK cell parameters. However, women in both experimental groups who reported positive changes in meaning-related goals over the study period also showed increases in NKCC. Results suggest that prioritizing goals emphasizing relationships, personal growth, and striving for meaning in life may have positive biological correlates but that solitary written disclosure may not be sufficient to induce changes in these goals in response to a past bereavement.

Although the possibility of sexual transmission of the hepatitis C virus (HCV) remains controversial, little is known of the associations ofpositive semen specimens with potential demographic and behavioral risk factors. Knowledge of these predictors may suggest factors that increase risk of HCV RNA in the semen. Semen and bloodfrom 80 HCV-infected homeless men were evaluatedfor the presence of HCVRNA by means of branch DNA and transcription-mediated amplification analyses. Associations of selected demographic and behavioral characteristics of the participants with presence or absence of HCV in their semen were also assessed. HCV RNA was detected in the semen of 36% of the sample. Associations were found with HCV RNA in semen and older age, higher viral loads of HCV in blood, current alcohol and lifetime methamphetamine use, and having been vaccinated for the hepatitis B virus. Findings suggest that sexual transmission of HCV is plausible and shed light on the need to conduct more in-depth investigations.

Objective: Fatigue is a common problem among cancer patients and survivors, yet the mechanisms underlying the occurrence and persistence of this symptom are not known. Activation of the immune system may evoke feelings of fatigue, which are mediated by proinflammatory cytokines. We examined whether fatigued breast cancer survivors would show elevations in proinflammatory cytokines and markers of cytokine activity compared with nonfatigued survivors. Differences in lymphocyte subsets, cortisol, and behavioral symptoms associated with proinflammatory cytokines were also assessed., Methods: Forty breast cancer survivors (20 fatigued, 20 nonfatigued) provided blood samples at visits scheduled to control for diurnal variability. Cytokines, soluble markers of cytokine activity, and cortisol were measured by immunoassay and lymphocyte subsets by flow cytometry. Participants also completed questionnaires measuring demographic, medical, and behavioral variables., Results: Fatigued breast cancer survivors had significantly higher serum levels of several markers associated with proinflammatory cytokine activity than nonfatigued survivors, including interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor type II (sTNF-RII), and neopterin. They were also more likely to report behavioral problems that co-occur with fatigue in the context of immune activation. Fatigued survivors had significantly lower serum levels of cortisol than the nonfatigued group as well as differences in two lymphocyte populations., Conclusions: Fatigued breast cancer survivors showed elevations in serum markers associated with proinflammatory cytokine activity an average of 5 years after diagnosis. Results suggest mechanisms through which enduring immune activation may occur, including alterations in cortisol and in lymphocyte subsets.

Neurotransmitters can accelerate HIV-1 replication in vitro, leading us to examine whether differences in autonomic nervous system (ANS) activity might promote residual HIV-1 replication in patients treated with highly active antiretroviral therapy. Patients who showed constitutively high levels of ANS activity before highly active antiretroviral therapy experienced poorer suppression of plasma viral load and poorer CD4(+) T cell recovery over 3-11 months of therapy. ANS activity was not related to demographic or behavioral characteristics that might influence pathogenesis. However, the ANS neurotransmitter norepinephrine enhanced replication of both CCR5- and CXCR4-tropic strains of HIV-1 in vitro via chemokine receptor up-regulation and enhanced viral gene expression, suggesting that neural activity may directly promote residual viral replication.

Idiopathic CD4+ T cell lymphocytopenia was unexpectedly detected in a 33-year-old, otherwise healthy young woman with no HIV or other viral infection, autoimmune, or neoplastic disease or increased susceptibility to infection. CD4+ T cell levels were 60-140/microl over a 3.5-year period. Following an uneventful pregnancy, the patient developed anemia and interstitial nephritis associated with a plasma cell dyscrasia with a monoclonal IgA gammopathy and a shifting immunoglobulin pattern that included IgG and IgA monoclonal proteins and increased urinary light chains. Osteolytic lesions were never detected and bone marrow aspirations revealed up to 10% atypical plasma cells. Various therapies often used in treating multiple myeloma only temporarily controlled the increasing renal damage. IL-2 therapy of 600,000 to 1 million units subcutaneously daily resulted in increased CD4+ T cells to normal levels, a decrease in the gammopathy, a return of renal function, energy, and weight gain, and apparently normal health status sustained for 2 years. The findings are compatible with a potentially fatal but nonmalignant immunoregulatory disorder that can be controlled by IL-2 administration., (Copyright 2001 Academic Press.)

A multicenter, double-blind, randomized, placebo-controlled study was conducted to determine the safety and efficacy of thalidomide in reduced, intermittent doses for preventing recurrences of oral and esophageal aphthous ulcers in patients with human immunodeficiency virus (HIV) infection. Forty-nine HIV-infected patients whose ulcers previously had healed as a result of thalidomide therapy were randomly assigned to receive either 100 mg of oral thalidomide or placebo 3 times per week for 6 months. Ulcers recurred in 14 (61%) of 23 thalidomide-randomized patients, compared with 11 (42%) of 26 placebo-randomized patients, with no significant difference in the median time to recurrence of ulcers (P=.221). There were no changes in plasma levels of HIV RNA, tumor necrosis factor (TNF)-alpha, and soluble TNF receptor II at the time of ulcer recurrence. Adverse events among patients treated with thalidomide included neutropenia (5 patients), rash (5 patients), and peripheral sensory neuropathy (3 patients). Thalidomide in lower intermittent doses is ineffective at preventing recurrence of aphthous ulcers in HIV-infected persons.

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.

An external evaluation program for measuring the performance of laboratories testing for cytokines and immune activation markers in biological fluids was developed. Cytokines, chemokines, soluble cytokine receptors, and other soluble markers of immune activation (CSM) were measured in plasma from a healthy human immunodeficiency virus (HIV)-seronegative reference population and from HIV-seropositive individuals as well as in supernatant fluids from in vitro-stimulated human immune cells. The 14 components measured were tumor necrosis factor (TNF) alpha, gamma interferon, interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, Rantes, MIP-Ia, MIP-Ibeta, soluble TNF receptor II, soluble IL-2 receptor alpha, beta(2)-microglobulin, and neopterin. Twelve laboratories associated with the Adult and Pediatric AIDS Clinical Trial Groups participated in the study. The performance features that were evaluated included intralaboratory variability, interlaboratory variability, comparison of reagent sources, and ability to detect CSM in the plasma of normal subjects as well as the changes occurring in disease. The principal findings were as follows: (i) on initial testing, i.e., before participating in the program, laboratories frequently differed markedly in their analytic results; (ii) the quality of testing of a CSM in individual participating laboratories could be assessed; (iii) most commercial kits allowed distinction between normal and abnormal plasma CSM levels and between supernatants of stimulated and unstimulated cells; (iv) different sources of reagents and reference standards frequently provided different absolute values; (v) inexperienced laboratories can benefit from participating in the program; (vi) laboratory performance improved during active participation in the program; and (vii) comparability between analyses conducted at different sites can be ensured by an external proficiency testing program.

Immune changes and their relationships in a frail elderly population (N=116, age 70-103, median 86 years) were defined in comparison to a healthy younger group. Previous immune studies in the elderly have generally focused on one or few parameters without correlation analyses. Furthermore, the study populations have been active elderly in relatively small numbers. A total of 33 immune parameters representing many aspects of the immune system were quantified. Most changes in the frail elderly were parallel to those reported in active elderly. A classification tree analysis revealed that increased plasma activation markers (neopterin and sTNF-R) and increased CD28 expression on CD8 T cells and proliferative response separated the aged and control populations. Statistical procedures utilizing principal components analyses, partial correlations and exploratory factor analyses all indicated that immunologic parameters in frail elderly are grouped in three major clusters of immunologic results. These involved (a) increased plasma levels of neopterin and sTNF receptor indicating elevated IFNgamma and TNF cytokine activity; (b) increased proportion of mature (CD45RO) versus naïve (CD45RA) T cells; and (c) a diverse group of related changes including impaired proliferative response, reduced T cells, CD28 and CD25 expression, B cell percentage and lower CD4:CD8 ratios and increased HLA-DR expression. These findings emphasize that several different groups of immune parameters but not 33 independent immune changes, occurred in the aged population.

Natural killer (NK) cells are reproducibly mobilized into the circulation in response to intense physical exercise or acute psychological stress, and altered expression of adhesion molecules potentially contributes to NK-cell mobilization. Studies of leukocyte mobilization during acute stress have used psychological stressors which facilitate tight experimental control but have limited applicability to everyday life. We therefore used a laboratory model of marital conflict as an experientially meaningful acute stressor to elucidate relationships among conflict, cardiovascular reactivity, and altered leukocyte phenotype and function. Forty-one ethnically diverse, nondistressed, healthy married couples were asked to discuss a specific problem in their marriage for 15 min. Blood pressure and heart rate were measured before, during, and after the discussion, and blood was remotely drawn at the same time points to quantify numbers of specific leukocyte subsets, NK-cell adhesion molecule expression, and NK cytotoxicity. Couples responded to the conflict task with cardiovascular reactivity; increases in the percentages of circulating NK cells and CD8(+) T cells and decreases in the percentage of circulating CD4(+) T cells; decreases in the percentage of NK cells that express L-selectin; and increases in NK-cell cytotoxicity without a commensurate increase in per-cell cytotoxicity. Rapid downregulation or shedding of L-selectin (CD62L) from NK cells did not contribute to their mobilization during conflict. Instead, CD62L(-) NK cells were mobilized while CD62L(+) NK cells were selectively retained in the vascular marginating pool and/or in extravascular tissue. From a broader perspective, the data support the hypothesis that altered trafficking of specific leukocyte subsets is an integral component of the fight-or-flight response to an acute stressor., (Copyright 2000 Academic Press.)