Marcelo Lopez

Nutritional Support in Alcoholic Cirrhotic Patients Improves Host Defenses

BACKGROUND Malnutrition is usual in patients with alcoholic liver disease and is associated with a poor outcome. Nutritional support decreases nutrition-associated complications. AIM To demonstrate that nutritional support in ambulatory alcoholic cirrhotic patients improves host defenses. METHODS Thirty-one male outpatients with alcoholic cirrhosis CHILD-PUGH B or C were included. Twenty-five subjects completed six months consuming daily a nutritional supplement (Ensure, 1000 Kcal and 35 g protein), in addition to their regular diet. At entrance and every three months, a clinical assessment, nutritional evaluation and indirect calorimetry were performed. Liver function tests and LPS-induced monocyte production of cytokines, salivary secretory IgA, lactulose/mannitol ratio and breath hydrogen tests were also measured in these intervals. Delayed cutaneous hypersensitivity and IgG and IgM antibody response to endotoxin were assessed at entrance and at the end of the study. RESULTS Patients drank 85% of the provided supplement as an average. REE, total body fat and serum albumin increased, basal breath hydrogen decreased and cellular immunity improved significantly during the follow up period (p< or =0.03). All the other parameters remained unchanged throughout the study. Six patients (16.2%) died during the study, five due to upper gastrointestinal bleeding. CONCLUSION Nutritional support in alcoholic cirrhotic patients improves nutritional status and cell mediated immunity.

Impaired interleukin-1 and tumor necrosis factor production in protein-calorie malnutrition

Abstract The capacity of malnourished infants to produce interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) was evaluated before and after nutritional rehabilitation. Ten marasmic patients without infectious diseases 2 to 8 months of age with −2.48±0.54 weight for age Z score (mean ± SD) were studied on admission, and after 4 month of nutritional therapy in a Closed Nutritional Recovery Center. Cytokines were induced by in vitro stimulation of blood mononuclear cells with lipopolysaccharide. IL-1β and TNF-α were determined in supernatants and cell lysates using an specific immunoassay. Low levels of released and cell-associated IL-1β were found on admission; mean±SEM values were 2.0±0.5 and 1.3±0.5 ng/ml, respectively. After nutritional rehabilitation, a significant increase of released and cell-associated IL-1β were observed: 5.4±0.8 and 3.7±0.3 ng/ml, (mean±SEM) respectively, p

Local and systemic liberation of proinflammatory cytokines in ulcerative colitis

Determination of plasma and tissue cytokinelevels in inflammatory bowel disease have frequentlyresulted in conflicting data. In the present study wedetermined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokinesinterleukin (IL)-1β, IL-6, interferon(IFN)-γ, and tumor-necrosis factor (TNF)-αliberated by peripheral blood mononuclear cells (PBMC)and lamina propria mononuclear cells (LPMC) after 48-hrculture with pokeweed mitogen (PWM). IL-1β, IL-6,IFN-γ and TNF-α in the supernatant weredetected by ELISA. Results show low basal levels ofIL-1β secretion by PBMC and LPMC, and a considerableincrease after mitogen stimulation. Basal IL-6production by PBMC was higher in UC patients than incontrols [2029 pg/ml, CI9 (–165 to4223) vs 572 pg/ml (–383 to 1527) respectively, P = 0.05] and also afterPWM activation [14,995 pg/ml (7759 -22230) vs 6598 pg/ml(3240-9956), respectively, P = 0.05]. In LPMC, nodifferences in IL-6 secretion were observed. TNF-α in activated PBMC of patients with UC was notsignificantly increased in relation to control (P =0.09). No constitutive secretion of IFN-γ wasobserved in mononuclear cells. IFN-γ levelssecreted by activated LPMC were lower in patients withUC than in controls [1571 pg/ml (–108 to 3251) vs7953 pg/ml (3851-12,055), respectively, P = 0.03]. Theseresults suggest that IL-6, IL-1β, and TNF-α participate as mediators in the inflammatoryphenomena observed in UC. Further studies are necessaryto evaluate the role of IFN-γ in thiscondition.

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Interleukin-6 production and deregulation of the hypothalamic-pituitary-adrenal axis in patients with major depressive disorders.

The present study was designed to determine whether an association exists between HPA activity and cytokine production in major depression (MD). In 9 patients with MD and 11 control subjects of both sexes, all drug-free, activity of the HPA axis was evaluated by circadian rhythm of plasma cortisol, 24-h free urinary cortisol, an overnight 1 mg dexamethasone suppression test, and an oCRF stimulation test. Spontaneous and LPS-stimulated production of IL-1β, IL-6, and TNFα by peripheral blood mononuclear cells were also determined. We found a significantly elevated spontaneous production of IL-6 in patients with MD (3541.2 ± 726.8 vs 380.4 ± 77.5 pg/mL in controls, p<0.05), while LPS-stimulated production was significantly lower in patients than in control subjects (19,867.7 ± 3649.2 vs 33,142.2 ± 15,47.2 pg/mL, p<0.05). The adrenocorticotropic hormone response to oCRF, evaluated as the area under the curve (AUCACTH) was significantly lower in patients than in control subjects (p=0.02). A positive correlation between AUCACTH and LPS-stimulated IL-6 secretion was observed in patients with MD (r=0.75, p<0.05) but not in controls. These findings suggest that the activation of the inflammatory response described in depression might be associated with long-term hyperactivity of the HPA axis.

Transferrin and iron salts modulate differently tumor necrosis factor-α secretion by cultured human mononuclear cells1–3

Abstract Iron is an essential element for the normal function of many biological processes, including the immune response and hematopoiesis. Since iron deficiency results in impaired cytokine production (TNF-α), we investigated if iron, bound to its transport protein transferrin or by itself, modulates the secretion of tumor necrosis factor-α (TNF-α) by circulating monocytes. In particular, we examined the effect of Tf-bound iron or ferric chloride (FeCl 3 ) in the secretion of TNF-α by cultured blood mononuclear cells (BMNC) obtained from women with either normal Fe status (n=10) or with iron deficiency (n=10). The addition of 30 μM Tf, either in its apo or holo form, to BMNC cultures derived from both normal and iron deficient subjects, induced a marked increase in TNF-α secretion by cells, to about 1.2–1.4 ng/mL. Similarly, the addition of μM amounts of FeCl 3 to normal BMNC resulted in a dose-dependent increase of TNF-α secretion. By contrast, BMNC from iron deficient subjects were unable to secrete TNF-α under similar conditions. Lipopolysaccharide (LPS) induced a maximal secretion of TNF-α (3.9 ± 0.6 ng/mL, mean ± SEM) in BMNC derived from both normal and iron deficient women, an indication that ID cells had the capacity to secrete TNF-α in response to a bacteriologic insult. However, the combined addition of LPS and iron-salt did not induce a further increase in TNF-α secretion. These findings indicate that iron modulates the in vitro secretion of TNF-α by human mononuclear cells through a process that depends both on the iron status of the subject and on the form in which iron is supplied. Moreover, transferrin also induces the secretion of TNF-α in a way apparently independent of its iron-donating capacity.

Increased cytokine production is associated with acute inflammation in cirrhotic alcoholic patients

Abstract The role of cytokines in the etiology of liver injury and their contribution to the systemic manifestations that occur in patients with liver disease, are not clearly understood. Aim: To study if serum levels and in vitro blood mononuclear cell (BMC) production of IL-Iβ and TNFα are related to the severity of alcoholic liver cirrhosis, and identify potential factors that can modify cytokine production in these patients. Serum levels, spontaneous and in vitro LPS stimulated BMC production of Interleukin-Iβ (IL-Iβ) and Tumor Necrosis Factor α (TNFα), were measured in 38 patients with alcoholic cirrhosis Child B or C, and nine normal volunteers. Serum levels and spontaneous in vitro production of IL-Iβ and TNFα were below detection limits. There were no differences between normal controls and Child B or C patients in LPS-stimulated production of IL-Iβ or TNFα. However eight patients with alcoholic hepatitis or infections superimposed on cirrhosis, had higher levels on LPS-stimulated BMC production of IL-Iβ (12.9 ± 5.8 ng/ml) and TNFα (4.9 ± 2.3 ng/ml) than the rest of cirrhotic patients (5.3 ± 3.5 and 1.8 ± 0.9 ng/ml). There was no association between IL-Iβ and TNFα BMC production and parameters of liver function or recent alcohol ingestion. Increased levels of IL-Iβ and TNFα production by stimulated BMC are associated with acute inflammatory events in cirrhotic alcoholic patients and not with the severity of liver disease.

Depressed Immune Response in Malnourished Rats Correlates with Increased Thymic Noradrenaline Level

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Lesiones focales hepáticas benignas: un hallazgo frecuente a la tomografía computada

BACKGROUND Multidetector computed tomography (MDCT) of the abdomen, with use of contrast medium, is able to detect and differentiate most focal liver lesions. AIM To determine the prevalence and features of benign focal liver lesions (BFLL) detected by abdominal MDCT. PATIENTS AND METHODS We reviewed the reports of contrast abdominal MDCT performed to outpatients between August 2011 and July 2012. Clinical data of examined patients and imaging findings in terms of description of the hepatic parenchyma and the presence of BFLL, were recorded. RESULTS Data from 1,184 studies were analyzed. Of these, 461 studies (38.4%) reported BFLL. The most prevalent lesions were simple cysts in 290 studies (24%) and hemangiomas in 61 studies (5.1%), granuloma-calcification in 39 (3.2%), focal nodular hyperplasia in 19 (1.6%) and one adenoma. If patients with known causes of liver disease were excluded, the prevalence of BFLL did not change substantially (lesions were found in 396 (37.5%) patients). Compared with livers with signs of damage, normal livers had more cystic lesions (27 and 16.2% respectively, p = 0.014) and hemangiomas (5.3 and 1.1% respectively, p = 0.043). CONCLUSIONS BFLL are very common findings in MDCT studies. Most of these lesions are simple cysts and hemangiomas.