Rosaria Alba Merendino

Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity?

Interleukin (IL)-18 is highly expressed in macrophages from human atherosclerotic plaques, suggesting its involvement in ischemic syndromes. We evaluated IL-18 and IL-18 binding protein (BP) in healthy centenarians, as longevity is characterized by a reduced incidence of ischemic events. For comparison, patients with chronic ischemic syndromes (CIS) were evaluated. Serum IL-18 and IL-18BP levels were measured by non-cross-reacting ELISA in 16 healthy centenarians and in two age-control populations, each of 18 healthy individuals aged 55.9+/-1.43 and 74.3+/-1.35, respectively, as well as in 23 CIS patients, and another cohort of 23 healthy subjects that were age- and sex-matched with CIS patients. Centenarians displayed significantly higher total IL-18 serum levels compared to each control group. Elevated IL-18 levels were also present in CIS patients. However, centenarians had a significant higher level of IL-18BP compared to the cohort of 23 controls (P=0.0014), and compared to CIS patients (P=0.043); as a result centenarians exhibited a lower level of free IL-18 than CIS patients. The present results indicate that quenching of IL-18 by IL-18BP may explain the apparent paradox of elevated serum IL-18 with no vascular signs in centenarians.

Interleukin-18 and CD30 serum levels in patients with moderate-severe depression

Interleukin-18 (IL-18), a pro-inflammatory cytokine that plays an important role in the T-cell-helper type 1 response, is a new member of the family of cytokines produced in the brain. CD30 is a marker of T-cell-helper type 2 lymphocytes. We evaluated IL-18 and CD30 serum levels in 10 patients affected by moderate-severe depression (MSD). We demonstrated for the first time that serum IL-18 levels of MSD patients were significantly higher than those of healthy donors. On the contrary, no significant difference was found between serum CD30 levels of MSD patients compared with those of healthy donors. These data strengthen the hypothesis that MSD disease is associated with an inflammatory response, mainly T-cell-helper type 1, and suggest an important role for IL-18 in the pathophysiology of MSD.

Age-related modifications in circulating IL-15 levels in humans.

Aging is associated to a progressive establishing of a chronic inflammatory state linked to a continuous long exposure to antigens. Since IL-15 stimulates the proliferation of memory T cells and the immunosenescence is characterized by accumulation of memory T cells and exhaustion of naive T cells, we analyzed IL-15 levels in sera from 30 ultralongeval subjects with respect to those from young and old adults. IL-15 levels were assayed by immunoenzymatic methods. Ultralongeval subjects displayed significantly higher IL-15 levels with respect to both young and old controls. No statistical difference was found between old and young controls. These findings may explain, at least in part, the characteristic increase of memory cells in immunosenescence and the capacity of the immune system of centenarians to defend itself from infections through immune-inflammatory responses.

Serum levels of interleukin‐18 and s‐ICAM‐1 in patients affected by psoriasis: preliminary considerations

Objective To find new aspects of the systemic involvement of the Immune System in psoriasis, we determined serum levels of interleukin‐18 (IL‐18) (Th1‐inducing factor cytokine), CD30 (Th2 marker) and sICAM‐1 (adhesion molecule). In addition we evaluated the correlation between these molecules and psoriasis area and severity index (PASI).

Incidence of sensitivity to Anisakis simplex in a risk population of fishermen/fishmongers

BACKGROUND Anisakis simplex, a fish and cephalopodes parasite, can cause either gastrointestinal symptoms or allergic reactions in humans on eating/handling contaminated fish. OBJECTIVE The aim of our study was to determine the capacity of Anisakis simplex to induce specific IgE production and allergic reactions following eating and handling fish in a population at risk. METHODS We determined the levels of total IgE, specific IgE, and eosinophil count in 28 fishermen/fishmongers (group A) and 15 healthy donors (group B). A skin prick test (SPT) with extracts from Anisakis and the most common species of fish in our country, were also carried out. RESULTS Specific IgE to Anisakis were found in 14 subjects of group A (13 of them had a positive SPT to the same extract) and none of group B (only one subject had a positive SPT). The SPT with fish extracts was positive in 4 patients of group A but in none of group B. Subjects in group A with specific IgE to Anisakis showed higher total IgE levels and eosinophil counts compared with either other individuals of the same group or to those of group B. CONCLUSIONS These results indicate that fishermen/fishmongers are a population at risk for Anisakis simplex sensitization and suggest that this kind of sensitization should also be investigated not only in subjects like fishermen/fishmongers who live in countries where fish is likely to be contaminated with Anisakis simplex parasites, but also in those who handle fish for other reasons.

Malondialdehyde in benign prostate hypertrophy: a useful marker?

Benign prostate hypertrophy (BPH) is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA) is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA) is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this end, 22 BPH patients and 22 healthy donors were enrolled. Data show an increase of MDA level in BPH patients and a positive correlation between PSA and MDA levels. In conclusion, we describe a previously unknown relationship between PSA and MDA as an index of inflammation and oxidative stress in BPH.

Involvement of Interleukin-18 in Patients on Maintenance Haemodialysis

Maintenance dialysis induces a clinical state of immunodeficiency. The pathway of circulating T cells from haemodialyzed patients is changed and characterized by an increase of Th1 cells. The unbalanced T helper differentiation derives from an altered regulation of interleukin-12 (IL-12), which represents an important inducer of Th1. IL-18 is a pro-inflammatory cytokine expressed by a variety of cell types that is structurally related to the Th1 family and shares biological properties with IL-12 as the promotion of Th1 responses. To explain the involvement of IL-18 in the typical disorders of dialysis, we analyzed IL-18 serum levels in a group of haemodialyzed patients. We enrolled 16 patients on chronic haemodialysis (HD) treatment for end-stage renal failure and 16 healthy volunteers as the control group. IL-18 levels were assessed by immunoenzymatic methods (detection limit was <12.5 pg/ml). HD patients strongly showed higher IL-18 serum levels compared to healthy donors (508.47 ± 314.39 vs. 193.44 ± 56.33 pg/ml, p < 0.005). Moreover, IL-18 levels in HD directly correlated to dialytic age (Rho = 0.544, p = 0.0419) and indirectly to Kt/V (Rho = 0.703, p = 0.0086). Our data represent the first evidence of the relation between IL-18 serum levels and HD. In the light of our results, we think that the unbalanced T helper differentiation may depend, at least in part, on an abnormality in the IL-18 production.

Interleukin-12 and interleukin-10 production by mononuclear phagocytic cells from breast cancer patients.

Interleukin-10 (IL-10) and Interleukin 12 (IL-12) generation may be regulated by a complex monocyte and macrophage-derived cytokine network and an impairment of the immune system can be observed in neoplastic disease. In this study, we examined the production of these cytokines by phagocytic cells, obtained from breast cancer (BCa)-bearing patients. Our results suggest that an increased IL-10 formation may represent an important regulatory pathway of IL-12 production by BCa mononuclear cells. In this report, we show that mononuclear cells of patients affected by breast cancer have a defective IL-12 production capability while generating higher amounts of IL-10.

Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease.

Parkinsons disease (PD) is an extra-pyramidal neurodegenerative disorder, in which alterations of the immune system are involved. Interleukin (IL)-15 stimulates cellular immune response and induces growth and differentiation of various immune cells. RANTES, promoting leukocyte infiltration to sites of inflammation, mediates the trafficking and homing of immune cells. To clarify the potential effect of levodopa on the immunological network of PD, we analyzed IL-15 and RANTES serum levels in PD patients, treated or not with levodopa, and in healthy donors. Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients. So, we hypothesize that the immunological alterations found in PD may be linked, at least in part, to levodopa therapy.

Relationship between IL-18 and sICAM-1 serum levels in patients affected by coeliac disease: preliminary considerations

OBJECTIVES Cytokine production from activated T cells play a pathogenetic role in mucosal lesions of coeliac disease (CD). Active interleukin (IL)-18 is expressed in the small intestinal mucosa in CD but not in healthy controls. IL-18 enhances intercellular adhesion molecule-1 (ICAM-1) expression. We analyzed IL-18 serum levels in CD patients before and after gluten-free diet and the possible correlation with soluble ICAM-1 (sICAM-1) serum levels. METHODS The study comprises ten CD patients before and after gluten free diet and ten healthy controls. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. RESULTS Serum IL-18 and sICAM-1 levels were significantly higher in patients with CD before diet with respect to healthy controls (P<0.05), with a highly significant correlation between the two parameters (Rho=0.800, P=0.0167). Gluten free diet significantly reduces IL-18 and sICAM-1. CONCLUSION Our findings show that IL-18 serum concentrations correlated with the clinical status of CD patients suggesting a role for this cytokine in the pathophysiology of this disease.