Protein carbonyl group content in patients affected by familiar chronic nail candidiasis.

Familiar chronic nail candidiasis (FCNC) is a rare disorder characterized by early-onset infections caused by different species of Candida, restricted to the nail of the hands and feet, and associated with a low serum concentration of intercellular adhesion molecule 1. Host defense mechanisms against candidiasis require the cooperation of many immune cells through several candidacidal mechanisms, including oxygen-dependent killing mechanisms, mediated by a superoxide anion radical myeloperoxidase--H2O2--halide system, and reactive nitrogen intermediates. We analyzed protein carbonyl groups (considered a useful marker of oxidative stress) in the serum of patients belonging to a five-generation Italian family with an isolated form of FCNC. Serum protein carbonyl groups in FCNC patients were significantly lower than those measured in healthy donors. Also, if this hypothesis is merely speculative, we could suggest that the decreased circulating level of protein carbonyl groups in these patients is not a marker of a lower oxidative stress condition, but might be linked to a lower protease activity.

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). BACKGROUND: Psoriasis is associated to an overexpression of Th1 cytokines and a relative underexpression of Th2 cytokines. IL-18 plays an important role in inducing Th1 response because it is a potent inductor of synthesis of IFN-gamma, TNF and other mediators. The two major sources of IL-18 are monocytes and macrophages but also human keratinocytes constitutively synthesized IL-18. SUBJECTS AND METHODS: We selected two groups of subjects: 16 healthy donors (HD) and 16 patients affected by psoriasis, matched for sex and age. Serum IL-18, CD30 and sICAM-1 levels were assayed by immunoenzymatic method with commercial kits. RESULTS: IL-18 and sICAM-1 levels in the patients were significantly higher than in the HDs (385.94 +/- 193.89 vs. 227.38 +/- 92.76 pg/mL, P = 0.005 and 445.00 +/- 152.67 vs. 317.88 +/- 107.20 ng/mL, P = 0.02, respectively). On the contrary, no significant difference was found between serum sCD30 levels of patients in respect to those of HDs. A significant correlation was found between serum IL-18 and PASI (Rho = 0.695, P = 0.0071), serum IL-18 and sICAM-1 (Rho = 0.543, P = 0.0356) and between sICAM-1 and PASI (Rho = 0.659, P = 0.0107).

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.

Influence of 5-fluorouracil and folinic acid on interleukin-18 production in colorectal cancer patients.

AIMS AND BACKGROUND: This study was carried out to evaluate the IL-18 blood concentrations of operated colorectal cancer patients and their possible variation in response to combination chemotherapy with 5-fluorouracil (5-FU) and folinic acid. METHODS: IL-18 levels were assayed in sera of 18 healthy donors and 18 surgical colorectal cancer patients before and after adjuvant chemotherapy with 5-fluorouracil and folinic acid. An ELISA kit for human IL-18 was used for the assay. RESULTS: Colorectal cancer patients showed significantly higher baseline levels of IL-18 than healthy donors (p<0.005). Furthermore, serum IL-18 levels increased significantly with respect to baseline in patients receiving adjuvant chemotherapy (p<0.005). CONCLUSIONS: This study suggests that treatment with 5-fluorouracil and folinic acid may provoke an increase in IL-18 serum levels in colorectal cancer patients. This increase may help to explain the efficacy of adjuvant chemotherapy with 5-FU in colorectal cancer.

Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study.

BACKGROUND: Specific immunotherapy is the only currently available allergen-orientated treatment able to modify the natural history of respiratory allergic diseases. Safety and clinical efficacy of this treatment are well documented, but evidence about the ability to reduce new sensitizations is still poor. OBJECTIVE: We report a retrospective study conducted in order to assess the prevention of new sensitizations in monosensitized subjects treated with specific immunotherapy vs. monosensitized patients treated with anti-allergic drugs. METHODS: 8396 monosensitized patients with respiratory symptoms were selected according to an open, retrospective design. Group A included 7182 patients submitted to specific immunotherapy (and anti-allergic drugs when needed) for 4 years and then treated with drugs for at least 3 years. Group B included 1214 patients treated only with drugs for at least 7 years. All patients underwent prick test with a standard panel of allergens and total and specific IgE determination before and after 4 years of treatment and again 3 years later. RESULTS: Groups were well balanced. Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4 years (P < 0.0001) and 26.95% and 76.77%, respectively, after 7 years (P < 0.0001). Asthmatic subjects were more prone to develop polysensitization in comparison to subjects suffering only from rhinitis (32.14% instead of 27.29% after 4 years, 36.5% instead of 31.33% after 7 years; P < 0.0001). Specific IgE decreased by 24.11% in Group A and increased by 23.87% in Group B (P < 0.0001). Total IgE decreased by 17.53% in Group A and increased by 13.71% in Group B (P < 0.0001). CONCLUSIONS: Specific immunotherapy was observed retrospectively to reduce new sensitizations in monosensitized subjects suffering from respiratory allergic diseases.

Serum levels of interleukin-18 and sICAM-1 in patients affected by breast cancer: preliminary considerations.

Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper type 1 response, acts as an angiogenesis and tumor suppressor. Intercellular adhesion molecule-1 (ICAM-1) has a potential role in immunoregulation by mediating immune cell infiltration into the tissue. The aim of this study was to evaluate IL-18 and soluble (s) ICAM-1 serum levels in breast cancer (BCa) patients with liver (BCaM1 h) or bone (BCaM1 b) metastases compared to BCa patients without metastases (BCaM0) and healthy donors (HDs). Furthermore, since IL-18 enhances ICAM-1 expression, we investigated whether there was a direct correlation between sICAM-1 and IL-18 serum levels. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. The serum sICAM-1 levels in the three groups of cancer patients were significantly higher (p<0.05) than those of HDs. Serum IL-18 levels were significantly higher (p<0.05) in BCaM1h and BCaM1b patients compared to BCaM0 patients and HDs. sICAM-1 proved to be closely correlated with serum IL-18 levels in HDs, whereas a weaker correlation was found in BCaM1h, BCaM1b and BCaM0 patients. The defective correlation between sICAM-1 and IL-18 found in cancer patients may contribute to our understanding of the immunity upset occurring in cancer. Our data suggest that IL-18, irrespective of its biological activity, could represent a marker for metastatic breast cancer.

Effect of fluticasone propionate on soluble CD30 release in patients with severe allergic asthma.

Previous studies have demonstrated improvements in health-related quality of life in asthmatic patients after treatment with fluticasone propionate. CD30 is a marker of Th2 lymphocytes, which are key cells in the pathogenesis of allergic inflammation. There is also a soluble form of CD30 (sCD30) released by CD30+ cells. Since serum sCD30 levels are high in allergic patients, in our study we examined the possible role of fluticasone propionate in modulating sCD30 release in patients with severe allergic asthma. In addition, we evaluated a possible correlation between sCD30 and FEV1 in these patients. To this end two groups of subjects were enrolled: 20 healthy nonatopic control subjects (group A) and 20 atopic patients with severe bronchial asthma receiving fluticasone propionate at the total dosage of 1 mg/day for 8 weeks (group B). Serum samples were examined before and after the treatment period. sCD30 serum levels were determined by the commercial ELISA-kit (Dako). The limit of detection of the assay was 1 U/ml. Our data show that sCD30 basal serum levels were significantly (p <0.05) higher in patients of group B respect to group A subjects (8.35+/-4.88 vs. <1 IU/ml, respectively). In addition, we found that sCD30 serum levels were undetectable in patients of group B after fluticasone propionate therapy. In group B a positive correlation between serum sCD30 levels and FEV1 values before fluticasone propionate treatment was noted (Rho = -0.644, p <0.005). The fluticasone propionate inhibition of sCD30 release may partly explain how fluticasone propionate exerts its antiinflammatory activity, through the modulation of Th2 cells.

Burning mouth syndrome due to cadmium in a denture wearer.

We report the case of a female denture wearer who was referred to our service due to burning of the lips and tongue but with no visible oral lesions. Her biochemical data, complete blood cell count, sedimentation rate, thyroid and sex hormones were normal. Tongue culture was negative. Patch tests, performed with a panel of 20 potential denture allergens, gave positive results (+++) only to a 2% petrolatum cadmium sulfate, which was present in the denture. Removal of the denture led to the clearing up of oral symptoms in 3 days. In light of these findings, carrying out patch tests with the allergens related to denture materials should be considered in these cases.

In vitro effect of lithium chloride on interleukin-15 production by monocytes from IL-breast cancer patients.

Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer. Interleukin-15 (IL-15) is a cytokine which possesses promoting activities on hematopoiesis and is also involved in antitumor response, activating NK, CTL and LAK cells. In this study we analyzed IL-15 production by monocyte cultures treated with lithium chloride (LiCl). Monocytes were obtained from patients affected by non-metastatic and metastatic breast cancer. LiCl treatment induced IL-15 production by monocytes mainly from non-metastatic patients. Combined lipopolysaccharide/LiCl treatment of monocyte cultures up-regulated IL-15 release compared to those treated with LPS alone (p<0.0001). The modulation of LiCl-induced IL-15 could counteract the immunosuppression state of cancer patients, which should be taken into account when developing new immunotherapeutic strategies.

Role of IL-15 on monocytic resistance to human herpesvirus 6 infection.

Interleukin-15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses. Recently, it has been demonstrated that Human Herpes virus type 6 (HHV-6) enhances NK activity of human PBMC by inducing IL-15. HHV-6 is a typical immunosuppressive agent, as suggested by its tropism for both CD4+ and CD8+ T cells, B cells, monocytes/macrophages, megakaryocytes and NK cells. Moreover, several studies have indicated that mononuclear phagocyte resistance to virus infection is influenced by the cellular differentiation state. This paper describes the effect of pretreatment "in vitro" with IL-15 on the resistance of human monocytes (HM) to HHV-6 infection. Our results demonstrate that undifferentiated HM were highly resistant to HHV-6 infection, whereas HM pretreated with human recombinant IL-15 showed an increased permissiveness for HHV-6 infection. This permissiveness was characterised by higher release of extracellular virus as well as an increased percentage of antigen positive cells. Moreover, we evaluated IL-15 production after the addition of HHV-6 to monocytes precultured in different experimental conditions. Our data indicate that HHV-6-induced IL-15 production by human monocytes is not affected by the condition of "in vitro" precultivation/differentiation. Furthermore, the neutralization of IL-15 induced by HHV-6 in differentiated monocytes did not affect viral replication. These findings suggest that IL-15 acts only on the mechanisms of cellular differentiation, rendering HM more susceptible to HHV-6 infection, without interfering with virus replication.

In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients.

AIMS AND BACKGROUND: Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuclear cells are defective in patients affected by neoplastic disease, we analyzed IL-8 production by monocytes obtained from patients with nonmetastatic breast cancer (BCaM0) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCl) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer and acute leukemia. Lithium influences the hematopoietic system, which is known to be regulated by numerous cytokines including IL-8. METHODS: We selected three groups of subjects (15 per group): patients affected by BCaM0, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiCl-treated monocyte cultures. RESULTS: Monocytes from BCaM1 released higher IL-8 levels than monocytes from BCaM0 (P <0.0001); the IL-8 levels of both groups were significantly higher (P <0.0001) than those of HD. In vitro LiCl treatment reduced IL-8 production by monocytes obtained from all subjects compared to the same cells when untreated or LPS treated. The suppressive effect of LiCl on IL-8 production by monocytes from breast cancer patients was particularly marked in monocytes from BCaM0 with respect to those from BCaM1. LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaM0 monocytes. Moreover, combined LPS/LiCl treatment of monocytes significantly (p <0.0001) downregulated the release of IL-8 compared to treatment with LPS alone. CONCLUSIONS: Our data demonstrate that monocytes from BCaM0 release larger amounts of IL-8 than monocytes from BCaM0 and from HD. Lithium was able to downregulate IL-8 production by monocytes from different subgroups. Further studies are needed to clarify if the improvement of the hematopoietic system in vivo observed following lithium therapy could reside, at least in part, in the ability of lithium to downregulate this chemokine.

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.

Aluminium allergy in a patient with occupational contact dermatitis.

Case of a 57-year-old hospital attendant with hand eczema. Patch tests were read at 2 and 3 days using the 1+ to 3+ scoring system recommended by the Contact Dermatitis Research Group.

Evaluation of interleukin-18 production by in vitro differentiated monocytes from breast cancer patients.

Interleukin-18 (IL-18) is a multifunctional cytokine which may play an important role in cancer. In previous studies it has been reported that mononuclear cells from breast cancer patients were defective in cytokine production. In this report we examined in vitro IL-18 release by monocytes (Mo) and differentiated monocytes (Mphi) for 6 or 12 days from healthy donors (HD) and nonmetastatic breast cancer (BCa) patients prior to chemo-, hormonal or radiotherapy. Our results show no production of this cytokine by Mo and Mphi for 6 days in all the experimental conditions. HD Mphi cultured for 12 days were responsive to lipopolysaccharides only after 24 h of treatment, while significantly (p<0.05) lower amounts of IL-18 were produced by BCa Mphi cultures in the same experimental conditions. Since BCa Mphi are defective in IL-18 production, and this cytokine elicits in vivo protective antitumor effects, we hypothesize a future possibility for the use of IL-18 in cancer therapy.