Delayed-type Hypersensitivity Skin Responses Research Articles

Long Term Cell Immune Response to COVID-19 Vaccines Assessment Using a Delayed-Type Hypersensitivity (DTH) Cutaneous Test.

Objective: As we progress with mass vaccination against SARS-CoV-2, there are key questions about the immunogenicity of COVID-19 vaccines that still are not answered. Conventional methods to measure cellular immune responses are complex and expensive in a pandemic situation. Patients and methods: Forty healthy healthcare workers accepted to participate during the vaccination schedule with a mRNA vaccine against SARS-CoV-2. Measurement of Delayed-Type Hypersensitivity (DTH) cutaneous response after intradermal test of protein S of SARS-CoV-2 at day 35 and day 200 was performed. At the same time, a specific anti-RBD IgG using a classic ELISA before vaccination, and on days 0, 35, and 200 was performed. Results: All 40 individuals had a positive DTH skin response at day 35, whereas 39 participants had a positive skin test at day 200. Moreover, although all 40 individuals showed a positive humoral response of specific IgG against spike protein at day 35, with most of them having significantly lower levels at day 200. Conclusion: DTH could be proposed as an ideal and easy method to predict cellular immunity response to mRNA vaccines 200 days after starting an immunization schedule with mRNA vaccine for COVID-19.

Abstract P2-13-29: Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer

Abstract Background: Delayed type hypersensitivity (DTH) skin tests in the randomized, active-controlled, single-blinded, multicenter Phase IIb trial investigating GLSI-100 (GP2+GM-CSF) administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) have been analyzed. The trial enrolled HLA-A*02 patients randomized to receive GLSI-100 versus GM-CSF alone. The trial's primary objective was to determine if treatment with GLSI-100, a HER2-derived peptide, reduces recurrence rates. Analyses for this trial showing GLSI-100 to be efficacious, safe and immunogenic have been previously reported by Patel et al. and Mittendorf et al.. Methods: Consented patients were randomized and scheduled to receive GLSI-100 (500 mcg GP2: 125 mcg GM-CSF) or control (GM-CSF only) via 6 intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for the first 6 months and 4 booster intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters. DTH skin tests were assessed at baseline and after the 6th dose with the orthogonal mean of each skin reaction measured 48-72 hours after injection using the sensitive ballpoint-pen method.. Results: The study enrolled 180 patients across 16 clinical sites with both HER2 3+ positive and low HER2 expressors (1-2+). After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GLSI-100, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). GLSI-100 was shown to be well tolerated with no SAEs deemed related to study medication and elicited a potent immune response measured by local skin tests and immunological assays. Injection site reactions were common, occurring in almost 100% of patients treated with either GLSI-100 or GM-CSF alone. Previous publications have reported the increase in DTH response reported among patients after treatment with GLSI-100. However, it was of interest to understand the positive DTH responses to GP2 noted at baseline. 22.8% of patients reacted to GP2 at baseline with induration of 5mm or greater. In the subgroup of patients who later experienced a breast cancer recurrence, 36.4% (8/22) had such a baseline response. Analysis of the time to recurrence among those recurring found that the median time to recurrence was 0.6 years for those with a baseline response while those that did not have a positive baseline DTH response to GP2 took 1.2 years to recur.. Conclusions: This study demonstrated that GLSI-100 safely elicited a potent immune response as evidenced by increased DTH skin responses with treatment paired with improved disease-free survival. It is theorized that a positive baseline DTH skin test to GP2 may be evidence of an existing immune response to GP2 associated with residual disease, impending recurrence, or prior treatments. Further studies assessing if GP2 immune response is an important prognosticator of cancer disease state or recurrence are planned. Citation Format: Snehal S Patel, David B McWilliams, Mira S Patel, Christine T Fischette, Jaye Thompson, F. Joseph Daugherty. Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-29.

Application of transdermal patches with new skin test reagents for detection of latent tuberculosis.

Introduction. Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.Aims. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.Methodology. Defined recombinant antigens that were unique to Mycobacterium tuberculosis (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and M. bovis bacille Calmette-Guérin (BCG) vaccine was evaluated.Results. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.Conclusion. Transdermal application of defined purified antigens might be a promising method for LTBI screening.

Immune Responses to Candidate Vaccine Antigens Delivered Through Naked Plasmid and Mycobacterial Vectors

Tuberculosis (TB) is a major global health problem and has been declared “a global emergency” by the World Health Organization. The failures of the currently available vaccine against TB, i.e. Mycobacterium bovis BCG, to impart consistent protection against TB, have led to the need for alternative vaccines. The low molecular weight major antigenic proteins, i.e. PE35, CFP10 and ESAT6, encoded by Mycobacterium tuberculosis-specific region of difference-1 (RD1) are among the antigens considered important to develop new TB vaccines. To deliver these antigens, two DNA vaccine vectors (pUMVC6 and pUMVC7) and three live mycobacterial species (M. bovis BCG, M. vaccae and M. smegmatis) were evaluated for the induction of antigen-specific cellular immune responses in animals. DNA corresponding to pe35, esat6 and cfp10 genes were amplified using polymerase chain reaction (PCR) from the genomic DNA of M. tuberculosis and cloned into plasmids pUMVC6 and pUMVC7 to prepare DNA vaccine constructs. Furthermore, the PCR-amplified DNA were cloned into a shuttle plasmid (pDE22), and the recombinant shuttle plasmids (pDE22-PE35, pDE22-CFP10 and pDE22-ESAT6) were electroporated into mycobacteria. The induction of antigen specific cellular immune responses was studied by immunizing mice and guinea-pigs with the recombinant constructs. The results with all the recombinant constructs and both animal models showed the consistent induction of antigen-specific cellular immune responses (spleen cell proliferation and secretion of protective T helper 1 cytokine interferon-γ in mice, and delayed-type hypersensitivity skin responses in guinea-pigs) only with the recombinant constructs expressing PE35 protein. These results suggest the superiority of PE35 antigen in inducing protective cellular immune responses in animals.

Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.

Recombinant proteins encoded by genes present in Mycobacterium tuberculosis-specific regions of difference induce delayed-type hypersensitivity skin responses (43.31)

Abstract The world-wide control of tuberculosis (TB) requires affordable and easy to apply test(s), which could differentiate TB from BCG vaccination and exposure to environmental mycobacteria. In this study, the proteins encoded by Mycobacterium tuberculosis-specific regions of difference (RD) genes, which are absent in BCG and most environmental mycobacteria, were studied for delayed-type hypersensitivity (DTH) skin responses in guinea pigs. The genes of RD1 (CFP10 and ESAT-6), RD7 (Rv2346 and Rv2347) and RD9 (Rv3619 and Rv3620) proteins were cloned in plasmid vectors and expressed in Escherichia coli. The expressed recombinant proteins were purified to homogeneity using affinity columns. Guinea pigs were injected with 1x1010 heat-killed M. tuberculosis, and phosphate buffered saline (PBS), as a placebo control. After four weeks of injection, all the animals were tested for DTH skin responses by intradermal injection with PBS (negative control), purified protein derivative (PPD) and sonicates of M. tuberculosis (positive control), and purified recombinant proteins. The results showed that PBS failed to induced DTH responses in any group, whereas PPD, M. tuberculosis sonicates and the recombinant proteins induced positive DTH responses in animals injected with heat-killed M. tuberculosis, but not in PBS-injected animals. These results suggest that purified RD proteins are active in inducing DTH responses in vivo, and may be useful in specific diagnosis of TB.

Epigallocatechin-3-Gallate Ameliorates Experimental Autoimmune Encephalomyelitis by Altering Balance among CD4 + T-Cell Subsets

The green tea component epigallocatechin-3-gallate (EGCG) may be beneficial in autoimmune diseases; however, the underlying mechanisms are not well understood. In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis, an animal model for human multiple sclerosis, and the underlying mechanisms. Female C57BL/6 mice were fed EGCG (0%, 0.15%, 0.3%, and 0.6% in diet) for 30 days and then immunized with specific antigen myelin oligodendrocyte glycoprotein 35-55. EGCG dose dependently attenuated clinical symptoms and pathological features (leukocyte infiltration and demyelination) in the central nervous system and inhibited antigen-specific T-cell proliferation and delayed-type hypersensitivity skin response. We further showed that EGCG reduced production of interferon-γ, IL-17, IL-6, IL-1β, and tumor necrosis factor-α; decreased types 1 and 17 helper T cells (Th1 and Th17, respectively); and increased regulatory T-cell populations in lymph nodes, the spleen, and the central nervous system. Moreover, EGCG inhibited expression of transcription factors T-box expressed in T cells and retinoid-related orphan receptor-γt, the specific transcription factor for Th1 and Th17 differentiation, respectively; the plasma levels of intercellular adhesion molecule 1; and CCR6 expression in CD4(+) T cells. These results indicate that EGCG may attenuate experimental autoimmune encephalomyelitis autoimmune response by inhibiting immune cell infiltration and modulating the balance among pro- and anti-autoimmune CD4(+) T-cell subsets. Thus, we identified a novel mechanism that underlies EGCG's beneficial effect in autoimmune disease.

The effect of selenium supplementation on DTH skin responses in healthy North American Men

The trace element selenium (Se) is essential for immune system development and function in animals. However, the exact functions of Se in the human immune system and the achievable health benefits from Se supplementation remain unclear. To test whether an increased intake of dietary Se affects immune function, we conducted a randomized, controlled trial of Se supplementation in healthy free-living men. Forty-two men were administered 300 μg of Se a day as high-Se Baker's yeast, or low-Se yeast for 48 weeks. Serum immunoglobulins, differential complete blood counts and lymphocyte sub-populations were measured every 6 weeks. Tests of delayed-type hypersensitivity (DTH) skin responses to mumps, candida, trychophyton, tuberculin-purified protein, and tetanus were performed at baseline and at the end of 48 weeks of treatment. Supplementation increased blood Se concentration by 50%. Surprisingly, consumption of the low-Se yeast induced anergy in DTH skin responses and increased counts of natural killer (NK) cells and T lymphocytes expressing both subunits of the high affinity interleukin-2 receptor (IL2R). DTH skin responses and IL2R+ cells did not change in the high-Se group, suggesting Se supplementation blocked induction of DTH anergy. There were no differences between groups in quality of life indicators, number of days sick, other leukocyte phenotypes, serum immunoglobulins, or complement factors. These results suggest that Se plays a role in immunotolerization, a cell-mediated process involved in many aspects of immune function.

Nutritional, immunological and health status of the elderly population living in poor neighbourhoods of Quito, Ecuador

The number of elderly people is increasing in less-developed countries. Although nutritional deficiencies and infectious diseases are generally more prevalent in resource-poor countries, the health and nutritional status of the elderly in South America in general, and in Ecuador, in particular, remains largely unstudied. The objective of the present study was to assess the nutritional, immunological and health status of elderly Ecuadorians. A cross-sectional study was conducted to evaluate a sample of elderly Ecuadorians with 24 h dietary recalls, biochemical and anthropometric measurements, delayed type hypersensitivity skin response and a health questionnaire. The 145 elders who enrolled had a mean age of 74.3 (SD 6.9) years. Of the subjects, 52 % exhibited BMI >or=25 kg/m(2), whereas 9.1 % had BMI <or=20 kg/m(2). Means of dietary intakes were below recommendations for most nutrients; exceptions were carbohydrate, fat, Fe and Se. Serum nutrient levels indicated that 50, 44, 43, 19 and 18 % of participants had deficiencies of Zn, Fe, vitamins B12 and D, and folate, respectively. The mean number of positive responses to seven recall antigens was 2.1 (SD 1.7) with an induration diameter of 9.9 (SD 7) mm, which are substantially lower than those reported for elders in developed countries. During the previous 6 months, 54 and 21 % of subjects reported at least one episode of respiratory infection or diarrhoea, respectively. Of these, 47 % sought care at a hospital or from a physician and 96 % from a relative or friend. In conclusion, while few elderly Ecuadorians were underweight, obesity was common. Micronutrient deficiencies were prevalent and may contribute to reduced immunological responses in this population.

Effect of Concomitant Consumption of Fish Oil and Vitamin E on T Cell Mediated Function in the Elderly: A Randomized Double-Blind Trial

Objectives: To determine if concomitant consumption of fish oil and vitamin E would modify the vitamin E level needed for improving T cell mediated function in elderly.Methods: A randomized and double-blind study was conducted using 40 healthy male and female elderly subjects (>65 y) who were randomly assigned to one of 4 groups (n = 10/group). All the subjects received 5 g of fish oil daily containing 1.5 g eicosapentaenoic acid (EPA) and 1 g docosahexaenoic acid (DHA), and a capsule containing different doses of dl-α-tocopherol (0, 100, 200 or 400 mg/day) for 3 mo. Plasma vitamin E and fatty acid levels, and in vivo [delayed-type hypersensitivity skin response (DTH) and T cell sub-population analysis] and ex vivo [mitogen-stimulated peripheral blood mononuclear cells (PBMC) proliferation and interleukin (IL)-2 production] immune functions were determined at baseline and after supplementation.Results: The control group (fish oil only) did not show a statistically significant change in either DTH or PBMC proliferation. DTH response, however, was significantly increased from baseline in all groups supplemented with fish oil plus vitamin E and a significant positive correlation between DTH response and plasma concentrations of α-tocopherol was observed. PBMC proliferation was only significantly increased in the group supplemented with fish oil plus 200 mg vitamin E. However, the changes caused by fish oil plus vitamin E in either DTH or PBMC proliferation were not significantly different from those observed in control group. Plasma levels of α-tocopherol were significantly increased in all three fish oil plus vitamin E groups and the increase in plasma α-tocopherol level was less profound than that previously reported when vitamin E was given alone.Conclusions: The immuno-enhancing effect of vitamin E in the elderly is dampened when it is concomitantly consumed with fish oil. This may be due to the smaller increase in plasma concentrations of vitamin E in the presence of fish oil.

Vitamin E and immune response in the aged: molecular mechanisms and clinical implications

Summary: Nutritional status has been indicated as a contributing factor to age‐related dysregulation of the immune response. Vitamin E, a lipid‐soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed‐type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)‐2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E2, a T‐cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell‐dividing and IL‐producing capacities of naïve T cells, but not memory T cells. The vitamin E‐induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naïve T‐cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

Vaccine efficacy of a cell lysate with recombinant baculovirus-expressed feline infectious peritonitis (FIP) virus nucleocapsid protein against progression of FIP

The Type II feline infectious peritonitis virus (FIPV) infection of feline macrophages is enhanced by a monoclonal antibody (MAb) to the S protein of FIPV. This antibody-dependent enhancement (ADE) activity increased with the MAb that showed a neutralizing activity with feline kidney cells, suggesting that there was a distinct correlation between ADE activity and the neutralizing activity. The close association between enhancing and neutralizing epitopes is an obstacle to developing a vaccine containing only neutralizing epitopes without enhancing epitopes. In this study, we immunized cats with cell lysate with recombinant baculovirus-expressed N protein of the Type I FIPV strain KU-2 with an adjuvant and investigated its preventive effect on the progression of FIP. Cats immunized with this vaccine produced antibodies against FIPV virion-derived N protein but did not produce virus-neutralizing antibodies. A delayed type hypersensitivity skin response to N protein was observed in these vaccinated cats, showing that cell mediated immunity against the FIPV antigen was induced. When these vaccinated cats were challenged with a high dose of heterologous FIPV, the survival rate was 75% (6/8), while the survival rate in the control group immunized with SF-9 cell-derived antigen was 12.5% (1/8). This study showed that immunization with the cell lysate with baculovirus-expressed N protein was effective in preventing the progression of FIP without inducing ADE of FIPV infection in cats.

Melanoma Vaccine--AVAX Technologies: DNP-VACC, M-Vax.

Melanoma Vaccine--AVAX Technologies: DNP-VACC, M-Vax.

Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects

We have shown that the age-associated increase in prostaglandin E(2) production contributes to the decline in T cell-mediated function with age. Black currant seed oil (BCSO), rich in both gamma-linolenic (18:3n-6) and alpha-linolenic (18:3n-3) acids, has been shown to modulate membrane lipid composition and eicosanoid production. Our objectives were to 1) test whether dietary supplementation with BCSO can improve the immune response of healthy elderly subjects, and 2) determine whether the altered immune response is mediated by a change in the factors closely associated with T cell activation. A randomized, double-blind, placebo-controlled (soybean oil) study was conducted to examine the effect of 2 mo of BCSO supplementation on the immune response of 40 healthy subjects aged >/=65 y. In vivo immune function was determined by delayed-type hypersensitivity skin response. Peripheral blood mononuclear cells (PBMCs) were tested for in vitro immune response. In subjects supplemented with BCSO, the total diameter of induration at 24 h and individual responses to tetanus toxoid and Trichophyton mentagrophytes were significantly higher than their baseline values. The change in response to tetanus toxoid was significantly different from that of the placebo group. The BCSO group showed a significant increase in proliferative response of PBMCs to the T cell mitogen phytohemagglutinin that was not significantly different from that observed in the placebo group. BCSO had no effect on concanavalin A-induced mitogenic response, interleukin 2 and -1beta production, and PBMC membrane fluidity. Prostaglandin E(2) production was significantly reduced in the BCSO-supplemented group, and this change was significantly different from that of the placebo group. BCSO has a moderate immune-enhancing effect attributable to its ability to reduce prostaglandin E(2) production.

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study

Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.

The relationship between fatigue, psychological and immunological variables in acute infectious illness.

The aim of this paper is to explore the longitudinal relationships between physical and psychological symptoms and immunological factors following acute infective illnesses. Preliminary data from a prospective investigation of patients with serologically proven acute infectious illnesses due to Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever are reported. Patients were assessed within 4 weeks of onset of symptoms and then reviewed 2 and 4 weeks later. Physical illness data were collected at interview. Psychological and somatic symptom profiles were assessed by standardised self-report questionnaires. Cell-mediated immune (CMI) function was assessed by measurement of delayed-type hypersensitivity (DTH) skin responses. Thirty patients who had been assessed and followed over the 4-week period (including 17 patients with EBV, five with RRV and eight with Q fever) were included in this analysis. During the acute phase, profound fatigue and malaise were the most common symptoms. Classical depressive and anxiety symptoms were not prominent. Initially, 46% of cases had no DTH skin response (i.e. cutaneous anergy) indicative of impaired cellular immunity. Over the 4-week period, there was a marked improvement in both somatic and psychological symptoms, although fatigue remained a prominent feature in 63% of subjects. The reduction in reported fatigue was correlated with improvement in the DTH skin response (p = 0.001) and with improvement in General Health Questionnaire (GHQ) scores (p < 0.01). Acute infectious illnesses are accompanied by a range of nonspecific somatic and psychological symptoms, particularly fatigue and malaise rather than anxiety and depression. Although improvement in several symptoms occurs rapidly, fatigue commonly remains a prominent complaint at 4 weeks. Resolution of fatigue is associated with improvement in cell-mediated immunity.

Immune response: Effects of operative stress in a pediatric model

Purpose: The purpose of this study is to delineate the effect of different operative procedures on the cell-mediated immune response in a pediatric animal model using the delayed type hypersensitivity (DTH) skin test. Methods: Sprague Dawley rats (1 week old) were sensitized against keyhole limpet hemocyanin (KLH). Animals were challenged 2 weeks later by an intradermal injection of KLH (0.3 mg) in sterile saline. Rats with positive DTH skin reactions at 24 and 48 hours after challenge (baseline) were divided randomly into five groups (n = 10 each): group I, unmanipulated control; group II, anesthesia; group III, anesthesia and midline extraperitoneal incision; Group IV, anesthesia and laparoscopy (pneumoperitoneum with carbon dioxide); Group V, anesthesia and midline laparotomy. Before each procedure (day 0) and on postoperative days 3 and 6, animals were again challenged intradermally with KLH (0.3 mg). DTH skin reaction was evaluated 24 and 48 hours later. Results: A statistically significant difference ( P < .05) in DTH skin reaction at 24 and 48 hours was observed between postoperative days 1 to 5 in the extraperitoneal and laparotomy groups with respect to baseline and the control group. Statistically significant differences were found in postoperative days 1, 4, and 5 between laparoscopy and laparotomy. The laparoscopy group showed a statistically significant decrease in DTH skin induration on postoperative day 2 when compared with the control group. At postoperative day 7 and 8 there was no statistical difference in DTH skin response comparing baseline values or between groups. Conclusions: These results suggest that in a pediatric animal model, abdominal surgical procedures accompanied by extensive tissue dissection produce a cellular immunosuppression, lasting up to 7 days, which is not observed in less invasive procedures. Observations concerning lesser immunosuppressive effects of laparoscopy when compared with laparotomy in adult models, as previously described by our laboratory, were also found in this pediatric model.

The Systemic Inflammatory Response to Cardiopulmonary Bypass

The Systemic Inflammatory Response to Cardiopulmonary Bypass

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. Historical cohort study. Bissau, Guinea-Bissau. 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: A preliminary report

We have previously demonstrated that at least 50% of patients with melancholia have impaired cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity (DTH) skin responses to a standardized battery of antigens. Hypercortisolaemia and increased circulating catecholamines both occur in patients with severe depressive disorders and each has been proposed as a possible mediator of observed immune abnormalities in patients with mood disorders. As part of a larger study, we collected 24 h urine samples from 28 patients with major depression and measured concentrations of urinary free cortisol (UFC), the noradrenaline metabolite dihydroxyphenylglycol (DHPG), adrenaline, and the dopamine metabolite DOPAC. CMI multitest skin testing revealed a reduced or absent response in 54% of subjects. Those with reduced DTH skin responses demonstrated increased urinary adrenaline ( P<0.02), with trends towards increased UFC ( P = 0.052) and increased DHPG ( P = 0.06). These differences could not be attributed to differences in age or depression severity. Correlational analyses demonstrated inverse associations between the extent of DTH responsiveness and 24 h levels of urinary adrenaline and DHPG, with similar trends evident for UFC and DOPAC. These results suggest that both circulating catecholamines and cortisol may play roles in the reduction of CMI in patients with severe depression.