Decrease In Total Lymphocyte Count Research Articles

Multiple-dose pharmacokinetics of cenerimod and the effect of charcoal on its elimination.

Cenerimod is a sphingosine-1-phosphate receptor 1 modulator that reduces tissue availability of circulating lymphocytes. The compound is in Phase3 development for the treatment of systemic lupus erythematosus. Its pharmacokinetic properties are characterized by slow absorption and multiphasic elimination with a long terminal half-life (t½), potentially caused by enterohepatic circulation (EHC). In this trial in healthy participants, oral cenerimod 0.5 and 4mg once daily was administered for 50 days, followed by oral administration of activated charcoal (ie, 50 mg every 12 h for 11 days, starting 24 h after the last cenerimod dose), to investigate the potential EHC of cenerimod and assess whether elimination of cenerimod can be accelerated. The multiple-dose pharmacokinetics, pharmacodynamics, safety, and tolerability of cenerimod were also evaluated. For both doses, peak plasma concentrations were reached 6 and 7h after dosing. Cenerimod accumulated approximately eightfold and (near) steady-state conditions were reached after 50 doses, resembling clinically meaningful exposure to cenerimod. The t½ following 0.5 and 4 mg of cenerimod was 767and 799 h (ie, 32 and 33 days) and 720 and 780h (ie, 30 and 33 days) with or without administration of charcoal, respectively, indicating no statistically significant difference. Therefore, charcoal did not accelerate cenerimod elimination suggesting that there is no EHC of cenerimod. A reversible, dose-dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated.

Correlation between Total Lymphocyte Count, C Reactive Protein, and Neutrophil Lymphocyte Ratio Levels with Gastrointestinal Manifestations in Covid-19 Patients Treated at Ulin Hospital, Banjarmasin

BACKGROUND: Coronavirus disease can affect the digestive system and cause gastrointestinal manifestations. The increase in C-reactive protein (CRP) correlates with the severity of the disease. The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic factor in the early screening of patients with COVID-19. A low lymphocyte count can also predict gastrointestinal involvement. AIM: This study aims to determine the correlation between TLC, CRP, and NLR levels on gastrointestinal manifestations in COVID-19 patients treated at Ulin General Hospital, Banjarmasin. METHODS: This study used a cross-sectional design. Data were taken consecutively using the medical records of confirmed COVID-19 patients with gastrointestinal manifestations. The number of subjects in this study was 88 patients. RESULTS: A decrease in TLC levels (<1740 g/dL) was not proven to have a significant correlation with gastrointestinal manifestations in COVID-19 patients (p = 0.176). Increased levels of CRP (>48 mg/L) had a significant correlation by 5.71 times compared to subjects who did not experience increased CRP (p < 0.00001). Increased levels of the NLR (>6 mg/L) had a significant correlation by 2.82 times compared to subjects who did not experience an increase in NLR (p = 0.032). CONCLISION: An increase in CRP levels >48 mg/L and levels of NLR >6, respectively, allowed the subject to experience gastrointestinal symptoms by 5.71 times and 2.82 times when infected with COVID-19, while a decrease in total lymphocyte count <1740 was not proven to have a significant correlation with gastrointestinal manifestations.

Preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after curative intent surgical resection

BackgroundPostoperative early recurrence (ER) in patients with pancreatic ductal adenocarcinoma (PDAC) is frequently encountered after curative intent surgery. Nonetheless, clinical significance and risk factors of ER after surgery for PDAC have not been extensively investigated. The aim of this study was to determine preoperative risk predictors for ER in patients with PDAC after upfront surgery. MethodsEighty-one consecutive patients with PDAC who underwent curative intent surgical resection at Kangbuk Samsung Hospital between January 2004 and May 2015 were enrolled. ER was defined as tumor relapse within 6 months after surgery. ResultsER occurred in 26 patients (32.1%), whereas 49 patients (60.5%) had late recurrence (≥ 6 months after surgery), and 6 patients had no recurrence (7.4%). Univariate analysis showed that C-reactive protein (CRP) > 3.0 mg/dL, modified Glasgow prognostic score (mGPS) = 2, decrease of total lymphocyte count by > 50% of baseline value in the preoperative period, prognostic nutritional index (PNI) < 45, neutrophil-to-lymphocyte ratio (NLR) ≥ 3, and preoperative maximum standardized uptake value (SUVmax) were significantly associated with ER. Multivariate logistic regression analysis revealed that CRP > 3.0 mg/dL, decrease of total lymphocyte count by > 50% of baseline value, and preoperative SUVmax were significant and independent contributors of ER in patients with resectable PDAC who underwent curative intent surgery. ConclusionsPostoperative ER for resectable PDAC was frequent with poor prognosis after curative intent upfront surgery. It is reasonable to suggest that there is a subgroup of resectable PDAC patients at high-risk of ER and neoadjuvant therapy should be considered in these patients in a clinical trial setting.

Regulatory CD4+ T lymphocytes after allogeneic transfusion in orthopaedic surgical patients.

Regulatory CD4+ T lymphocytes after allogeneic transfusion in orthopaedic surgical patients.

Multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an S1P1receptor modulator: Favorable impact of dose up-titration

This multiple-ascending-dose study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an S1P1 receptor modulator and a potential new treatment for autoimmune diseases. In part A, 10 healthy male and female subjects received once daily oral doses of ponesimod (5, 10, or 20 mg) or placebo for 7 days. Sinus bradycardia and, in some subjects, atrioventricular (AV) block occurred primarily on the first day of dosing, as desensitization developed to ponesimod-induced heart rate (HR) reduction and PR-prolongation. This elicited the design of an up-titration schedule in 17 subjects to a dose of 40 mg in part B. The up-titration regimen reduced HR and PQ/PR effects. Reported adverse events were mainly related to the cardiac and respiratory systems. Respiratory effects increased with higher doses. Ponesimod multiple-dose pharmacokinetics were slightly more than dose-proportional and characterized by a time to maximum concentration and an elimination half-life varying from 2.5 to 4.0 hours and 30.9 to 33.5 hours, respectively, and an accumulation of about 2.3-fold. Ponesimod caused a dose-dependent sustained decrease in total lymphocyte count, reversible within 7 days of discontinuation. A pharmacokinetic-pharmacodynamic model enabled comparing day 1 and steady-state conditions. These results warrant further investigation of ponesimod in patients.

Omega-3 fatty acid supplementation, nutritional status and quality of life in patients with gastrointestinal cancer: double-blind, placebo-controlled, randomized study

Introduction: Cancer cachexia is characterized by weight loss, immunosuppression and is associated with worse prognosis and quality of life. Objectives: To evaluate the effect of ω-3 supplementation on nutritional status, functional capacity and quality of life of patients with gastrointestinal cancer. Methods: the placebo group (P) (n = 10) received seven 1,000 mg capsules of soybean oil and the supplement group (S) (n = 11) seven 1,000 mg capsules of fish oil and flaxseed containing 214.3 mg of eicosapentaenoic acid and 113.5 mg of docosahexaenoic acid daily for 14 days. We evaluated weight, body composition, inflammatory and immunological markers, functional capacity and quality of life. Results: The average weight variation of the P group before and after treatment was -0.44 ± 2.7 kg and of S group was 0.07 ± 1.4 kg, with no statistical difference. The average BMI of the sample was 20.5 ± 3.4 kg / m 2. There was a significant reduction of total serum protein (p = 0.005) and albumin (p = 0.011) in the P group; and an increase in levels of C-reactive protein (CRP) (p = 0.005) and decrease in total lymphocyte count (p = 0.037). An increase in serum transfer

Impact of Major Orthopedic Surgery On Regulatory CD4+ T Lymphocytes and Cytokines in Transfused and Non-Transfused Patients.

AbstractAbstract 2286It is known that major surgery and allogeneic blood transfusion mediate immunosuppression by interfering on cytokine secretion, lymphocyte count and cytotoxic response. However, which cytokines and lymphocyte subpopulations participate in such immunosuppressive state remains poorly understood. Regulatory T cells (Tregs) are suppressive CD4(+) cells with a central role in immunosuppression of trauma victims, cancer patients, and transplant recipients. Several markers have been identified with regulatory properties, such as FOXP3, CTLA-4, GITR and the recently described CD69. Recently, allogeneic blood transfusion has been shown capable of inducing regulatory CD4+FOXP3+ T cells in vitro. Purpose:In this study, we aimed to investigate regulatory CD4+ T cells induction and cytokine profile in transfused and non-transfused surgical patients. Patients and Methods:Thirty-five patients undergoing elective hip replacement were recruited for this study and prospectively evaluated. Blood samples were obtained before surgery (D0) and on days 1 (D1) and 4 (D4) after surgery. Quantification of regulatory T lymphocytes was done by flow cytometry using CD4, CD25, FoxP3, CTLA-4, GITR and CD69, while cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ and TGF-β) levels were determined by multiplexed immunoassay system. Results:From the 35 patients recruited for this study, 18 (51.4%) received allogeneic non-leukodepleted red cells transfusion during or after surgery. There were no significant differences in clinical or epidemiological characteristics between transfused and non-transfused groups, except for the duration of surgery, being longer in transfused patients (p<0.001). Results of total lymphocyte count and subsets of CD4+ T cells in the 35 patients are summarized in the table:D0D1D4p valueTotal lymphocyte count (×109/mL)*1,907 (1579-2472)1,450 (1205-1864)1,266 (1092-1817)D0 vs. D1; p<0.001D0 vs. D4; p<0.001CD4+ (%)**24.5±9.833.3±11.738±11.7D0 vs. D1; p<0.001D0 vs. D4; p<0.001D1 vs. D4; p<0.001CD4+CD25-CD69+ (%)*0.55 (0.27-0.77)0.6 (0.3-1.23)1.13 (0.56-2.52)D0 vs. D4; p<0.001D1 vs. D4; p<0.001CD4+GITR+ (%)**1.64±1.642.92±1.944.38±3.00D0 vs. D1; p<0.001D0 vs. D4; p<0.001D1 vs. D4; p<0.001CD4+CTLA-4+ (%)*0.53 (0.46-0.97)0.89 (0.72-1.3)0.89 (0.64-1.33)D0 vs. D1; p<0.001D0 vs. D4; p<0.001*Results reported as median (P25-P75);**Results reported as mean±SDThe total lymphocyte count was significantly decreased only in transfused patients. No significant difference was seen in the percentage of CD4+CD25highFoxp3+ T lymphocytes by comparing days D0, D1 and D4. However, a significant increase of CD4+CD25-CD69+ cells was observed by comparing D1 vs. D4 [0.61(0.23–2.69) vs. 2.27 (0.64–4.45); p=0.001] in transfused patients, but not in the group of non-transfused patients [0.36(0.31–0.81) vs. 1.02(0.42–1.52); D1 vs. D4. Similarly, we also detected a significant increase in the number of CD4+GITR+ T cells in the group of transfused patients [D1 vs. D4; 3.12±2.01 vs. 5.19±3.33; p=0.007). Total hip replacement also led to substantial increase of the following cytokines: IL-6 (p<0.001, D0 vs. D1 and p<0.001, D0 vs. D4), IL-8 (p<0.001, D0 vs. D1 and p=0.017, D0 vs. D4), IL-10 (p<0.001, D0 vs. D1). However, no differences regarding cytokines levels were seen comparing groups of transfused and non-transfused patients. Conclusions:This study demonstrated that although allogeneic non-leukodepleted red cells transfusion is associated with decrease of total lymphocyte count following major surgery, there was a significant increase of total CD4+ T lymphocytes with no difference observed in transfused and non-transfused patients. However, a significant increase of CD4+CD25-CD69+ and CD4+GITR+ T lymphocytes was observed in the transfused group on D4, possibly reflecting the late effect of transfusion on induction of these subsets of CD4+ regulatory cells. The increase of pro-inflammatory IL-6, IL-8 and anti-inflammatory IL-10 levels indirectly highlights the imbalance on immune response after surgical trauma. Further studies, with a larger cohort and functional assays, investigating these CD4+ T cells subpopulations following major surgery and the impact of allogeneic non-leukodepleted red cells transfusion on these cells should be addressed. Disclosures:No relevant conflicts of interest to declare.

Acute Effect Of Propofol On Polymorphonuclear Neutrophils Burst Respiration

Surgical stress is followed by profound endocrine and metabolic changes, which have been demonstrated to influence the host defence response by direct effect on the immune system or activating the hypothalamic–pituitaryadrenal axis and the sympathetic nervous system [123]. Several investigators have studied the effect of stressful events on immune function. They were able to show that a variety of stresses, including surgery and pain, induced alterations of immune function in vivo, thus resulting in increased susceptibility to infection and tumour progression [45]. Concern about the impact of anaesthetics and sedatives used for general anaesthesia and in intensive care medicine is growing because of an increasing number of immunosuppressed patients require anaesthesia and intensive care treatment. The autonomic nervous system and the hypothalamicpituitary-adrenal axis provide an interface between stress and other organ systems [1]. Thus, anaesthetics may influence immune function by merely reducing the stress response. Phagocytosis and burst activity of polymorphonuclear neutrophils (PMNs) are essential to the bacterial and fungal killing capacity of the host. In surgical patients, an attenuated up regulation of cytokine secretion was observed together with a decrease in total lymphocyte counts and function. [67]. These alterations were positively correlated with the duration of surgery and the blood loss volume [6]. Surgical stress depressed monocyte mCD14 expression and human leukocyte antigen-DR expression. The concentration of the anti-inflammatory cytokine IL-10 increased, whereas the endotoxin-induced TNF-a production was suppressed [8]. Treatment with antiIL-10 antibodies partially restored the endotoxin-induced TNF-a production, indicating that IL-10 participates in this hyporesponsiveness[9]. The aim of this study is to investigate the acute effect of propofol on the respiratory burst of PMNs.

Increased apoptosis of peripheral blood mononuclear cells (PBMC) during general and epidural anaesthesia in dogs

The objective of the study was to investigate the hypothesis that perioperative lymphocytopenia was due to apoptosis of these cells induced by either halothane or epidural anaesthesia in dogs. The relationship between apoptosis induction and plasma concentrations of the stress hormone cortisol and the cytokines TNF-alpha and IL-10 was examined as well. The study was performed on 22 healthy mongrel dogs, equal numbers from both genders, weighing 18.3 +/- 2.9 kg, and aged between 3-5 years. Dogs were divided in three groups. Eight of the animals were anaesthetized with halothane, another eight received epidural anaesthesia using lidocaine, and six served as controls. Venous blood samples were obtained immediately before (0 minute) anaesthesia, during deep anaesthesia (120 minute), and on the next day (24 hour) in order to determine the following parameters: the total lymphocyte counts, the percentage of apoptotic peripheral blood mononuclear cells (PBMC) by flow cytometry, plasma concentrations of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay (ELISA), and plasma cortisol levels by radioimmune assay. Both halothane and epidural anaesthesia in dogs induces apoptosis of PBMC with slight decrease in total lymphocyte counts. These immunomodulatory effects were transient and faded till the 24th hour. Concerning the mechanism of inducing lymphocyte apoptosis by general or epidural anaesthesia, it seemed that neither cortisol, nor the tested cytokines TNF-alpha and IL-10 were implicated in this process. Further investigations are necessary to confirm this assumption.

Early T Cell Recovery of Thymus-Derived Naive T Cells and NK Cells in Pediatrics Patients after T-Cell Depleted HLA-Haploidentical Stem Cell Transplantation for Thalassemia.

Delayed immune recovery post transplant remains a significant obstacle and results in increased risk of infections. T cells are regenerated via 2 pathway, thymus-derived and peripheral expansion, processes for which IL-7 is critical. To analyse the mechanisms involved in immunological reconstitution, we studied six thalassemia patients after 20 and 60 days post T-cell-depleted HLA-haploidentical stem cell transplantation. The mean age ranged from 14 to 5 years. As controls, 6 healthy donors matched by sex and age with the patients were included. We analysed T cell subsets by flow cytometry. Stromal cells, obtained from long term culture of bone marrow mononuclear cells were analysed by immunohystochemistry and the stromal IL-7 production was analysed by ELISA. Day + 20 post transplant, the patients had significantly lower CD4+ T cells in comparison to the controls (1.9 ± 1.4% vs. 47.5 ± 6% respectively), and this reduced number was mainly observed in CD45RA+CD62L+ (naive phenotype) subset (1.3 ± 2% in patients vs. 52 ± 12% in controls). A significant decrease of peripheral CD45RA+CD31+ Th cells (thymic naive Th cells) (on average 0.5 ± 0.3% in patients vs. 37 ± 10% in controls) was observed, whereas CD8+ T cells numbers did not statistically differ between patients and controls (24.2 ± 33.7% vs. 20 ± 7%). NK cells were among the first lymphocytes to repopulate the peripheral blood, and up to 70% of these cells were CD56 bright whereas CD56dim CD16+ NK cells were reduced. Day + 60 post transplant an increase in the percentages of CD4+ T cells, naïve CD4+ cells and in thymic naïve Th cells were observed (3 ± 1.2%, 2.9 ± 2.1%, 2.7 ± 1%, respectively). CD8+ T cells were also increased (in mean 35 ± 27.5%). Compared with normal subjects, thalassemia patients showed a significant increase of CD4+ cell activation markers (CD95, HLA-DR and CCR5) and this was observed after 60 days post transplant, in parallel with the increase of the CD56dim CD16+ NK cells especially in the patients with full engraftment. Stromal cells secreted lower IL-7 levels (0.3 + 0.1 pg/mL vs. 0.8 + 0.1 pg/mL, in controls) and displayed by immunohistochemistry an altered phenotype (“macrophage-like” morphology). A significant decrease in total lymphocyte counts and depletion of CD4+ T cells expressing predominantly the CD45RA+CD62L+ phenotype were observed after 60 days post transplant. Also the CD4+CD45RA+CD31+ T cell subset was initially reduced but an increase has been observed at day + 60 post transplant, suggesting a thymus involvement in these patients. An IL7/IL7R pathway dysregulation has been also observed, possibly involving bone marrow stromal cells. NK cells were among the earliest lymphocytes to repopulate the peripheral blood, but. CD56dim CD16+ NK cells were increased after 60 days post transplant, especially in the patients with full engraftment, suggesting a role of donor NK cells on bone marrow engraftment. We hypothesize that the recovery of T cell compartment may be due to a deregulated production of new T cells starting from haematopoietic stem cells under the influence of stromal cytokines production.

Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients

Background/Aims: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8 + and CD4 + T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. Methods: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3 +CD8 + and CD3 +CD4 + subsets. Results: The patients studied showed a significant decrease of total lymphocyte count, T CD4 +CD3 +, CD28 +, CD8 +CD28 + lymphocytes and natural killer (NK) CD56 +CD16 +CD3 − cells. The reduction of CD28 + and CD8 +CD28 + lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3 +CD8 + subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. Conclusions: The association of a decreased number of T CD8 + cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.

Lymphopenia in occupational pulmonary silicosis with or without autoimmune disease.

An increased prevalence of autoimmune diseases such as rheumatoid arthritis has been demonstrated in silica-exposed patients. The aim of this study was to determine the peripheral blood lymphocyte phenotype in a population of silicotic workers employed in the slate mines of the district. Silicosis was assessed in 58 patients according to the International Labor Office's criteria. Clinical and biological data including flow cytometric evaluation of the lymphocyte subsets were compared with those from 41 healthy volunteers. The silicotic patients had a higher prevalence of autoimmune diseases (6/58 versus 0/41: P < 0.05) and of elevated antinuclear antibody titres compared to the control group. A very significant decrease of total lymphocyte count (P < 0.001) involving B, T and Natural Killer cells was found in silicotic patients as compared with matched healthy volunteers. A significant increase in the percentage of activated T cells (12.3%) was observed in the silicotic group as compared to 6.5% in the control group (P = 5 x 10(-5)). Our results show that in silicotic patients, the absolute number of circulating lymphocytes is diminished with an increased proportion of activated T cells. Whether these findings could predispose to the development of autoimmune disorders is discussed.

Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9 000 000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.

Primary HIV Infection and the Acute Retroviral Syndrome: The Urgent Need for Recognition

The new widespread availability of HIV viral-load testing, along with potent new antiviral therapeutic regimens, has created the opportunity for very early detection and treatment of acute HIV infection. It is critical that clinicians rapidly recognize primary HIV infection and consider the therapeutic options available during this early stage of disease. Recent evidence is a basis for hope that very early therapy will improve prognosis and perhaps even eradicate HIV. The period between initial exposure to and infection by HIV and the development of an HIV-specific antibody response is generally defined as primary HIV infection. Natural history during this stage of infection is characterized by both an enormous viremia and a vigorous immune response.1 During the peak period of viremia a rapid decline in CD4 cell count occurs. In six subjects studied by Cooper et al., all subjects had an initial decrease in total lymphocyte count. The lowest median CD4 and CD8 counts occurred nine days after the onset of clinical illness. Cooper also described a second phase of response to acute HIV infection, notable for an inversion of the CD4 to CD8 ratio. In the six subjects studied, the median inversion of CD4 to CD8 ratio occurred 16 days after the onset of clinical symptoms and the median value of the inverted ratio was 0.70. This inversion of ratio was secondary to an increase in the number of CD8 cells relative to CD4 lymphocytes and was temporally associated with the development of lymphadenopathy. A third phase of lymphocyte dynamics was noted to occur a median of 33 days after the onset of the clinical syndrome. The hallmark of this stage was an absolute increase in the number of circulating CD8 lymphocytes, resulting in an even greater inversion of the CD4 to CD8 ratio and probably reflecting a vigorous …

Nutritional status of HIV-infected patients during the early disease stages

Nutritional status was monitored in two groups of patients infected with human immunodeficiency virus (HIV) for up to 16 months. Twenty-six subjects were recruited from patients enrolled in acquired immunodeficiency syndrome treatment protocols in the early stages of the disease. Body weight, percent body fat, serum albumin, total protein concentration, hemoglobin, hematocrit, and total lymphocyte count were monitored monthly. Four-day food intake records were kept every 4 months. In the 19 patients followed for 16 months (Group 1), a significant (p less than .05) decrease was observed in body weight, percent body fat, body mass index (BMI), and total protein concentration. Seven subjects (Group 2), with more advanced disease than Group 1, demonstrated a significant (p less than .05) decrease in total lymphocyte count over a 5-month period. This latter group fell just below the normal range for hemoglobin and hematocrit concentrations during the study period. With the exception of a decrease in vitamin B-6, zinc, and total energy intake, food records closely matched the Recommended Dietary Allowance for the age group. Thus, we conclude that decreases in body weight, percent body fat, and BMI may be the earliest indication of decreased nutritional status in HIV-infected patients.

Lymphocyte Subpopulation Monitoring in Cyclosporine-Treated Patients Following Heart Transplantation

Circulating lymphocyte subpopulations were studied in 18 consecutive patients treated with cyclosporine-prednisone immunosuppression during the first month following heart transplantation. Eleven patients showed no evidence of graft rejection. There were eight episodes of acute rejection demonstrated at endomyocardial biopsy in 7 patients. Three patients were treated with corticosteroids, 3 were treated with rabbit antithymocyte globulin (RATG), and 1 died before treatment (early mortality: 5.6%). Using the monoclonal antibody technique, 150 determinations of lymphocyte subpopulations were performed and were correlated with 72 endomyocardial biopsy specimens. Cyclosporine immunosuppression caused a significant ( p < 0.05) decrease in total lymphocyte count (38%) and in the number of OKT3 (52%) and OKT4 cells (55%). During acute rejection, total lymphocytes and OKT3, OKT4, and OKT8 cells all increased significantly, but the T4 to T8 ratio did not change significantly. Treatment of rejection with corticosteroids resulted in a moderate but not significant decrease in all T-cell types, whereas RATG caused a marked but not selective decrease in all T-cell groups. In conclusion, T cells decrease with cyclosporine immunosuppression and with treatment of rejection and increase at onset of rejection, but the T4 to T8 ratio has no predictive value for the diagnosis and severity of rejection, and the sensitivity of the method does not permit its use to assess the degree of immunosuppression with cyclosporine following heart transplantation.

Acute-phase decrease of T lymphocyte subsets in rhinovirus infection.

Populations of peripheral blood leukocytes were enumerated in 15 volunteers challenged by intranasal inoculation with rhinovirus serotype 25. The results demonstrated a significant decrease in total lymphocyte count among infected persons on the third day after challenge with the virus (P less than .01). The change in lymphocyte count was associated with a significant decrease in total T cells, as determined by monoclonal antibodies (both T11+ and T3+, P less than .02), but not in B cells (B7+). Among the subsets of T cells, T4+ (T helper/inducer) and T8+ (T suppressor/cytotoxic) lymphocytes both declined in number, but only the change in the T4+ subset was significant. For each of the lymphocyte populations that decreased significantly (T3+, T11+, and T4+) there was a strong correlation with increased severity of symptoms. Persons who had the greatest decrease in total lymphocyte count also shed virus most frequently. The number of nonlymphocyte leukocytes increased with the severity of the symptoms. These data show that T lymphocytes (particularly the T4+ population) are related to both the progression of infection and the symptoms of the rhinovirus common cold.

Subacute sclerosing panencephalitis: influence of the clinical course and treatment with isoprinosine on non-specific cell-mediated and humoral immunity.

Cell-mediated and humoral immunity were studied in 30 patients with subacute sclerosing panencephalitis (SSPE). Marked changes in cell-mediated immunity were observed, manifested as a decrease in total lymphocyte count, decrease of proportion of T cells forming late E rosettes, depression in lymphocyte blastogenesis, production of migration inhibition factor and delayed-type skin reactivity. The humoral immune responses was not so markedly changed and only increased levels of serum IgG, IgM and the C3c fragment of complement were noticed. The changes in immunity were more pronounced in patients with a more advanced stage of the disease. 19 patients were investigated 3 times at 7-week intervals during treatment with isoprinosine. In the group of patients (10 cases) whose clinical status was rapidly deteriorating, a marked decline of cell-mediated immunity was observed. In the group of patients showing a stationary course of the disease, cellular immunity was improving. The mechanism of the disturbances of non-specific immunity in SSPE and the influence of isoprinosine on the immune answer are discussed.

Immunological observations on patients with acute cerebral vascular disease

Cell-mediated and humoral immunity was studied in 74 patients with acute cerebral vascular disease. During the first two days after the onset of disease marked changes of cell-mediated immunity were observed, manifested as a decrease in total lymphocyte count in the peripheral blood, decrease in number of T lymphocytes, depression in lymphocyte blastogenesis and production of the migration inhibition factor, and a delayed-type skin reactivity. The changes were most evident in patients with severe lesions of brain tissue resulting from primary cerebral haemorrhage and cerebral infarction with fatal outcome. In the group of patients with cerebral infarction with improvement of neurological symptoms the immunological changes were not so pronounced as in the two above-mentioned groups, the smallest changes being found in patients with subarachnoid haemorrhage. We suppose that the depression in the immune function was caused by severe stress during the course of disease. Impairment of the immune function may increase susceptibility to infection. The humoral immune response was not so evidently changed, and the observed increase of IgA in the sera was probably present before the stroke. In cases with good clinical course some improvement in the immunological parameters was observed, but full recovery did not occur until 3 weeks after the onset of disease.

Effect of operation on B and T lymphocyte counts

Preoperative and postoperative studies of peripheral B and T lymphocyte counts were accomplished in 21 patients. Diagnoses included 10 carcinoma of the breast, 3 sarcoma, and 8 benign diseases. On postoperative day one and two, an increase in B-cell percentage was observed in the majority of patients tested. However, there was a decrease in total lymphocyte count and fast-reacting T lymphocyte numbers on postoperative day one, especially in patients who had intraabdominal operations. All the lymphocyte counts returned to preoperative range within one week. Pertinent reports in the literature were reviewed and discussed.