Increased peripheral mononuclear cells expression of adhesion molecules in alcoholic cirrhosis: its relation to immune activation.

BACKGROUND/AIMS: Cell adhesion phenomena are relevant in the immune mechanisms leading to organ damage in various diseases. Patients with alcoholic cirrhosis present with immune alterations that include findings of immunodeficiency and indications of an activated immune response. METHODS: In 37 patients with alcoholic cirrhosis we have determined the expression of surface antigens and adhesion molecules on peripheral lymphocytes and monocytes, serum levels of immunoglobulins, circulating cytokines, namely tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta, serum soluble intercellular adhesion molecule and neopterin. RESULTS: In patients, we found an increased expression of several adhesion molecules ICAM-1, LFA-3 and MAC-1 in lymphocytes, LFA-3 in monocytes and surface activation markers CD71 and DR in lymphocytes, as well as increased concentrations of the serum parameters measured: IgA, IgG, IgM, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, soluble ICAM-1 and neopterin, in comparison with controls. CONCLUSIONS: The enhancement of the adhesion phenomena in circulating mononuclear cells of patients with cirrhosis correlates to the severity of the disease and is related to other parameters of immune activation.

T-cell activation, expression of adhesion molecules and response to ethanol in alcoholic cirrhosis.

Abnormal immune function is a well-recognized feature in patients with alcoholic cirrhosis. It may contribute to the pathogenesis of the disease and to the clinical consequences. Nevertheless, a potential role of ethanol to elicit immune disturbances in patients is still unclear. To further examine the immune mechanisms which potentially are involved in alcoholic cirrhosis and the relationship to ethanol, we have determined the expression of surface antigens CD4, CD8, and of adhesion molecules CD25, LFA-1, ICAM-1 and LFA-3 in patients and in response to stimulation with OKT-3, IL-2 and with ethanol in vitro. In addition, we quantified the production of IL-2, TNF-alpha and IFN-gamma by lymphocytes of alcoholic cirrhosis patients compared to controls. Lymphocytes from patients showed increased basal and stimulated expression of CD4, CD25, LFA-1, ICAM-1 and LFA-3 molecules and increased TNF-alpha production in comparison to controls. When lymphocytes from patients were co-cultured with ethanol, the overexpression of activation markers and TNF-alpha production was similar to that obtained with mitogens. In contrast, a predominant suppressive effect of ethanol was observed in lymphocytes from controls. Our study underlines the importance of a chronic state of immune activation in alcoholic cirrhosis. The data further suggest a role of ethanol to stimulate immune response and to be directly involved in the development of disease.

Neopterin and soluble tumor necrosis factor receptor type I in alcohol-induced cirrhosis.

Alcohol-induced cirrhosis (AC) is accompanied by disturbances of immune function and cytokine production. To better define the pattern of cytokine synthesis in this disease and to relate it to the immune activation state, we measured circulating levels of soluble tumor necrosis factor receptor p55 (sTNFR-55) and neopterin in a group of 85 patients with AC (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy volunteers. Serum concentrations of sTNFR-55 and neopterin were significantly raised in patients with AC. Moreover, concentrations of sTNFR-55 were significantly higher in patients with more severe disease compared with the group with lower severity. There were significant correlations between sTNFR-55 and neopterin levels in patients and controls. The results contribute to affirm the existence of an immune activation state in AC that could be responsible for the development of the disease and clinical complications.

Tumour necrosis factor, interleukin-1 and interleukin-6 in alcoholic cirrhosis.

The existence of a cellular immune deficit in alcoholic cirrhosis, and the alterations described in cytokine synthesis in this disease, led us to compare serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in a group of 33 patients with alcoholic cirrhosis (classified according to the Child-Pugh grade of severity of liver disease) and 43 healthy volunteers. Serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 were significantly raised in alcoholic cirrhosis patients, with no significant differences between patients with liver disease of different grades of severity. The results suggest that cirrhosis involves the activation of the monocyte-macrophage system, which may contribute to the progression of the disease and its clinical manifestations.

Low serum levels of alpha-interferon, gamma-interferon, and interleukin-2 in alcoholic cirrhosis.

The existence of cellular immune deficit in alcoholic cirrhosis, together with the role of alpha- and gamma-interferon and interleukin-2 in the immune system, led us to compare serum levels of these immune system mediators in a group of 40 patients with alcoholic cirrhosis classified according to Child-Pugh's grade of severity of liver disease and 23 healthy volunteers. Serum levels of alpha-IFN, gamma-IFN, and IL-2 were significantly depressed in alcoholic cirrhotics, with no significant differences between the different degrees of hepatic damage. The results suggest a profound alteration in the immune system of alcoholic cirrhotics, which may contribute to the development of the disease and the accompanying immune system deficit.

[Lymphocyte subpopulations in rheumatoid arthritis patients, their relatives and spouses]. / Subpoblaciones linfocitarias en pacientes con artritis reumatoide, sus familiares y cónyuges.

A study of lymphocytic sub-populations of patients with rheumatoid arthritis, their families and partners, is presented. The determination was carried out by means of monoclonal antibodies, analysing: T cells sub-population (CD3, CD4, CD8 and quotient CD4/CD8); B cells sub-population (B1); activated cells (OK1a); monocytes and NK cells (OKM1 and BMA 070). The results showed an increase of CD3 sub-population (T total lymphocytes) in patients with RA and their families. The meaning of these results is difficult to evaluate as lymphocyte sub-population is affected by several variables. The lack of modification of suppressor population, CD4/CD8 quotient and IKM1 cells in RA patients is probably due to the moderate activity of the disease.

[HLA antigens in patients with rheumatoid arthritis, their relatives, and spouses]. / Estudio de los antígenos HLA en pacientes con artritis reumatoide, sus familiares y cónyuges.

The results of the comparison between phenotypic frequency of HLA antigen classes I and II in patients afflicted with rheumatoid arthritis (RA) and their relatives (study carried out in the east of Andalusian), showed a significant increase of HLA A24, B51, B44, CW1 ans CW5 class I antigen in the group of relatives. We found a statistically significant DR4 antigen class II increase in both, patients and relative groups. The marriage parther of patients with RA did not have variations in class I or II HLA antigens compared to the control group. We concluded that RA is probably related to the following antigens: A24, B51, B44, CW1, CW5 and DR4.