Pharmacological immunomodulation of surgical trauma.

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.

Estado inmunológico de ancianos candidatos a artroplastia tras fractura subcapital de cadera: estudio de su relación con la edad y con la morbimortalidad postoperatoria* / Immunological status of elderly patients eligible for arthroplasty after a femoral neck fracture: relationship between the patients' status, their age and postoperative morbimortality

Objetivo. Analizar la relación de la situación inmunológica preoperatoria tras fractura subcapital de cadera con las complicaciones postoperatorias. Material y método. Estudio prospectivo aleatorio de 94 pacientes (81 mujeres) con fractura subcapital de cadera Garden IV (edad media: 82,9 años (± 7,48), máximo: 100, mínimo: 64 años). Al ingreso se determinó en sangre venosa periférica: fórmula leucocitaria, inmunoglobulinas (IgG, IgA, IgM e IgE), CD19, CD3, CD4, CD8, niveles de transferrina, alfa-2-macroglobulina, ceruloplasmina, proteína transportadora de retinol, prealbúmina, albúmina, proteínas totales, colesterol total y triglicéridos. Se estudiaron las complicaciones postoperatorias. En la estadística se realizó análisis de la varianza y Chi cuadrado. Resultados. Se detectaron 12 casos de infección de la herida quirúrgica, 27 casos de infección de orina, 3 casos de neumonía y una infección periprotésica. Los pacientes con infección postoperatoria presentaron en el preoperatorio menores niveles de IgM (infección de orina y neumonía), de IgA (neumonía) y de IgE (infección de la herida), menor número de CD4 y CD8/mm3 (infección de orina y neumonía) y un menor porcentaje de CD19 (infección de herida). La albúmina, la prealbúmina, el colesterol total, los triglicéridos y la transferrina disminuyeron significativamente con la edad. Conclusiones. La IgM, la IgA, la IgE, el porcentaje de CD19 y el número de CD4 y CD8 podrían servir como indicadores de un mayor riesgo de desarrollar infecciones durante el postoperatorio de una fractura subcapital de cadera

Purpose. To analyze the relationship between a patient's immunological status prior to arthroplasty secondary to a femoral neck fracture and postoperative complications. Materials and methods. Prospective randomized study of 94 patients (81 of which female) with a Garden IV femoral neck fracture (mean age: 82.9 years (± 7.48), range: 100-64). On admission, the following parameters were evaluated in the patients' peripheral venous blood: differential leukocyte count; inmunoglobulin (IgG, IgA, IgM and IgE); percentage of CD19, CD3, CD4 and CD8; transferrin levels; alfa-2-macroglobulin; ceruloplasmin; retinol transport protein; prealbumin; albumin; total proteins; total cholesterol and triglycerides. Postoperative complications were studied. Statistics: Variance and chi square analysis. Results. There were twelve cases of surgical wound infection, 27 of urinary infection, 3 cases of pneumonia and one periprosthetic infection. Patients with a postoperative infection had lower preop levels of IgM (urinary infection and pneumonia), IgA (pneumonia) and IgE (wound infection), as well as a lower count of CD4 and CD8 per cubic mm (urinary infection and pneumonia) and a lower percentage of CD19 (wound infection). Albumin, prealbumin, total cholesterol, triglycerides and transferrin decreased significantly with age. Conclusions. The IgM, IgA, IgE, the CD19 percentage and CD4 and CD8 counts could be used indicators of a higher risk of developing infections after surgery for a femoral neck fracture (AU)

Apoptosis and CD8 and CD54 cell expression in rat small bowel transplantation.

The importance of activated CD8 cells expressing IL-2R in small bowel and other organ rejection has been reported. Some authors even consider that a positive correlation might be demonstrated between the number of apoptotic enterocytes and the degree of graft rejection. In addition, moderate to intense activation of endothelial molecules in small bowel allograft in rats has been reported in chronic rejection. The aim of the present paper is to ascertain, in a heterotopic small bowel transplantation (HSBT) in rats, whether CD3, CD4, CD8, and CD54 cell expression in the allograft infiltrates shows some relationship with allograft enterocyte apoptosis when rejection is present. Wistar Furth male rats were allotted to two groups: group A was the control group without transplantation; group B received a heterotopic small bowel allograft from Fisher rats and an im dose of FK506 (0.25 mg/kg/day). A significant increase of CD8, CD54 cell receptor expression, and apoptosis in the group undergoing HSBT showed rejection. No significant differences have been observed in the variables under study between the control and HSBT without rejection groups or in CD3 and CD4 among the three groups. We observed a significant correlation between apoptosis and rejection, between CD8 and CD54 with apoptosis and with rejection, and between CD8 and CD54. This indicates that the activation of endothelial molecules and cells may play an important role in established HSBT chronic rejection. We consider that this study may contribute to the knowledge of small bowel allograft chronic rejection and its immunomodulation.

Determination of the immunoglobulin E postoperative variation as a measure of surgical injury.

The aim of this study was to ascertain postoperative changes in immunoglobulin E (IgE) in patients undergoing different types of surgery and the possible correlation with the duration and type of surgery. Evidence suggests that surgery induces a predominant activation pattern through the T-helper-2 (Th2) cell pathway, increasing interleukins (IL-4, IL-5, IL-10, IL-13), inhibiting Th1 cell activation, and promoting B and Th2 cell activation. IgE production may indicate predominant Th2 pathway activation and may be a more persistent and easily measurable postoperative marker than IL-6 for measuring surgical trauma. Altogether, 180 patients undergoing different types of surgery for nonneoplastic and nonparasitic diseases were studied. All patients received the same type of anesthesia. Before surgery and on the first (1PO) and 7th (7PO) postoperative days we determined in peripheral blood the CD3, CD4, CD8, CD16, and CD19 cell percentages; IL-1, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF) levels; and the IgA, IgG, IgM, total IgE, C3, C4, and CIC levels. On 1PO, all variables decreased except IgE, IL-1, IL-2, IL-4, IL-6, CIC, and CD19. Only IgE, IL-6, and CD19 increases showed a significantly statistical (ss) difference regarding preoperative values (0.01, 0.05, 0.001, respectively). Relations between the IL-4 and IgE increases (p < 0.01) and between the IgG decrease and IgE increase (p < 0.001) were found. On 7PO, only IgE was increased (p < 0.001). The IgE increase correlated with surgical trauma intensity (p < 0.05). We concluded that IgE increases during the early postoperative period, correlating with surgical injury intensity. The increase in the IgE level may be detected 24 hours after surgery and during the first 7 postoperative days depending on the type of surgery.

S-adenosylmethionine immunomodulator treatment in sepsis.

BACKGROUND: S-adenosylmethionine (SAMe) is a forerunner of glutathione. AIMS: The aim of the present study is to ascertain this drug effect on T-lymphocytes and cytokines in an experimental model of surgical sepsis. METHODS: Rats were allotted in two groups. In the control group, rats underwent anaesthesia and laparatomy with cecal ligation and puncture (CLP). In the second group, rats underwent the same CLP and received SAMe (14 mg/kg) i.m., on the 1st (1PO) and 2nd (2PO) postoperative days. A week before surgery (PRE), on the 1PO and on the 3PO: IL-1, IL-2, IL-4, IL-6, IL-10 and TNF levels (ELISA & MoAb), and CD3, CD4, CD8 cell and IL-2R percentages (%) (flow cytometry & MoAb) were determined in peripheral blood. RESULTS: Rats receiving SAMe do not show changes of CD3%, CD4% and IL-1 levels but show a significant increase of CD8% on the 3PO, showing a significant difference with regard to controls (p < 0.01). Both groups show a similar IL-2R variation pattern: increasing on 1PO (p < 0.05) and decreasing on 3PO (p < 0.05). CONCLUSION: In sepsis: SAMe inhibits the decrease of circulating immune-active cells and the IL-1 increase. This drug seems to have effects useful in avoiding immunological alterations in sepsis, that need to be tested in humans.

Immune response and in vivo production of cytokines in patients with liver hydatidosis.

Cytokines play an important role in the human immunological response, but the exact role of cytokines in the human immune response against parasites, especially against Echinococcus granulosus, remains unclear. IL-1, IL-2, IL-4 and tumour necrosis factor (TNF) levels in peripheral blood of 21 patients with liver hydatidosis were evaluated before surgical treatment, and the levels of IgA, IgM, IgG, IgE, specific IgE against E. granulosus, C3, C4 and DF complement fractions and CD20, CD3, CD4, CD8 and CD16 cell percentages were also determined, as was the relationship between these variables and cytokine levels. Data from hydatid patients were compared with data obtained from 21 healthy volunteers. Hydatid patients showed increases of IgG, IgE, IgEs and IL-2 (P < 0.01), and decreases of IL-1 and TNF levels (P < 0.001), but these variables (respectively) increased in patients showing cysts in the central area of the liver or with a wide opening of cysts in the biliary tract. The increase of IL-1, IL-2 and IL-4 showed a close relationship with the number, characteristics and above all the location of cysts within the liver itself. IgG and IL-4 levels and also IgG and IgE levels showed a significant correlation (P < 0.05).

Changes in blood lymphocyte populations in experimental bowel allograft rejection.

The aim of this study is to measure percentages of lymphocyte populations and IL-2R cellular expression in peripheral blood during the rejection of a small bowel allograft (SBA) in the rat. Thirty rats were allotted to three groups: A, control, no transplantation (Tx); B, rats receiving an orthotopic SBA; C, similar SBA but with thymostimulin (TP-1) administered before Tx, aimed at increasing the intensity of and accelerating rejection. The percentages of CD19, CD5, CD4 and CD8 cells and of IL-2R were determined when rejection was present. Rejection appeared in rats in group B between days 11 and 26 post-Tx and in group C between days 6 and 7 post-Tx (P < 0.001). In both B and C groups, CD5 and CD4 cells decreased (P < 0.005) and CD8 cells increased (P < 0.001). A correlation between CD8 and IL-2R content was found (P < 0.05). In group C, earliness of rejection correlated with the percentage of CD8 cells (P < 0.05) and the intensity of rejection with numbers of CD8 and CD19 cells (P < 0.05).