Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients.

Infection risk, sepsis and mortality after severe burn are primarily determined by patient age, burn size, and depth. Whether genetic differences contribute to otherwise unexpected variability in outcomes is unknown. We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis. We evaluated 71 patients with burns ≥15% TBSA and 109 healthy subjects. The genotypes of IL-6 (-174C/G), IL-10 (-819C/T and -1082A/G) and IL-17 (7488T/C) polymorphisms were identified applying polymerase chain reaction protocols. The cytokine levels in serum were determined with enzyme-linked immunoabsorbent assays. Our results demonstrated no significant differences in the genotype frequencies studied between burn patients and healthy subjects. No significant associations were found among IL-6 and IL-17F genotypes and the related cytokine serum levels. Only IL-10 promoter -1082GG genotype was related to an increased IL-10 production in burned patients. In addition, septic subjects bearing -1082G/G genotype have shown the highest and non-septic bearing -1082A/* genotypes the lowest IL-10 serum levels. All together these data seem to indicate that genetically determined individual difference in IL-10 production might influence the susceptibility to septic complications in burned patients and suggest that these markers might be useful in burned patient management.

Blocking TNF in vitro with infliximab determines the inhibition of expansion and interferon gamma production of Vgamma9/Vdelta2 T lymphocytes from patients with active rheumatoid arthritis. A role in the susceptibility to tuberculosis?

BACKGROUND: Side effects of TNF neutralisation - mostly infectious complications - were recognized, the most important being pulmonary tuberculosis infections. gamma/ d T cells contribute to protective immune response against mycobacterium tuberculosis. OBJECTIVES: The aim of the present study was to assess the expansion capacity of Vgamma9/Vdelta2 T cells from (tuberculin purified protein derivative (PPD) positive and PPD negative) patients with active rheumatoid arthritis (RA), and to examine the in vitro effect of infliximab on this lymphocyte subset. METHODS: 28 PPD negative RA patients were studied and compared with 14 PPD positive RA patients, 45 PPD-negative and 110 PPD-positive healthy volunteers. Cell separation, expansion in vitro of Vgamma9/Vdelta2 T lymphocytes (EF) and the expression of tumor necrosis factor receptor II and IFN-gamma content by Vgamma9/Vdelta2 T lymphocytes were studied before and after infliximab in vitro addiction. RESULTS: The EF from PPD positive subjects was higher than that from PPD negatives. Patients with RA have the highest levels. The addition of infliximab to the cultures from PPD-positive patients determined a significant inhibition of cell expansion and TNF RII expression and a significant decrease of IFN gamma content. CONCLUSION: In this study we have documented that gamma/ delta T lymphocytes from patients with PPD positive rheumatoid arthritis have a high capacity to respond in vitro to phosphoantingens with expansion TNF-RII expression and IFN gamma production that is inhibited by the exposure to infliximab. These results might be of relevance in view of the effect of TNF blocking on the pulmonary tuberculosis infection.

Pentoxifylline inhibits Vgamma9/Vdelta2 T lymphocyte activation of patients with active Behçets disease in vitro.

The aim of this study is to evaluate the in vitro effect of pentoxifylline (PTX) on T Vgamma9/Vdelta2 lymphocyte function in Behçets disease (BD). We investigated the effect of PTX on Vgamma9/Vdelta2 T cell expansion and expression of TNFRII receptor and perforin content before and after PTX addition by means of FACS analysis lymphocyte cultures from patients with active and inactive BD and healthy subjects. The addition of PTX at a concentration of 1 mg/ml determined a significant inhibition of cell expansion, a down regulation of TNF receptor expression and inhibited the PMA-induced degranulation of perforin. Taken together these data indicate that PTX is capable of interfering with Vgamma9/Vdelta2 T cell function in BD, and although cell culture models cannot reliably predict all of the potential effects of the drug in vivo, our results encourage the possibility that this drug may find use in a range of immunological disorder characterized by dysregulated cell-mediated immunity.

Humoral and cell mediated immune response to cow's milk proteins in Behçet's disease.

OBJECTIVE: To investigate the humoral and cellular immune response against cow's milk proteins in Behçet's disease and to distinguish any behaviour during active or inactive disease. METHODS: Peripheral blood mononuclear cells from 16 patients and from eight normal controls were cultured in the presence of phytohaemagglutinin (PHA), beta-casein, beta-lactoglobulin, or chicken egg albumin. Interferon gamma (IFNgamma) and interleukin 4 (IL4) were measured in the culture supernatants by enzyme linked immunosorbent assay (ELISA). Serum samples from 46 patients with Behçet's disease and from 37 healthy subjects were also studied for antibody detection. Antibodies to beta-casein, beta-lactoglobulin, and chicken egg albumin were determined by ELISA. RESULTS: High IFNgamma but not IL4 levels were found in the supernatants of lymphocytes from patients with active disease cultured in the presence of cow's milk proteins. Levels were comparable with those obtained in cultures stimulated with PHA. A significantly higher level of anti-beta-casein and anti-beta-lactoglobulin IgG and IgA antibodies was found in patients with active Behçet's disease. No relation was found between their occurrence and the age of the patients, the duration of disease, or the presence of gastrointestinal abnormalities. Antibodies to chicken albumin were detected at low levels and with a prevalence similar to that of healthy subjects. CONCLUSION: The results indicate that an active immune response occurs in Behçet's disease. This response involves an increased frequency of antibodies to cow's milk protein and a strong Th1 polarisation after exposure to these antigens. The occurrence of these abnormalities supports a putative role for cow's milk proteins immune response in the pathogenesis of Behçet's disease.