Body composition and -174G/C interleukin-6 promoter gene polymorphism: association with progression of insulin resistance in normal weight obese syndrome.

Insulin resistance and obesity are intimately related to a chronic low grade systemic inflammation. Interleukin-6 (IL-6) may influence the pathogenesis of obesity-related diseases. The aim of this study is to investigate the effect of body's fat mass on the relationships between -174G/C IL-6 promoter gene polymorphism, IL-6 circulating level and insulin resistance. A population of 150 Caucasian women was studied, subdivided according to their body composition in non-obese (NW), Normal Weight Obese (NWO) and preobese-obese (OB). The NWO subjects were found in an intermediate position between the NW and OB subjects in terms of body weight, fat mass percentage (FM%), abdominal FAT%, hs-CRP and plasma triglyceride level. Fasting plasma IL-6 concentration was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) in all subjects analyzed (P=0.0014). In NWO and OB women a significantly increased IL-6 mean value was observed compared with NW subjects. In G/G population, the IL-6 plasma level of NWO and OB was significantly higher with respect to NW. No significant differences of IL-6 concentrations were observed in the three groups carrying G/C genotype. NWO and OB women homozygous for the allele C have significantly lower value of IL-6 with respect to NW subjects. IL-6 concentration was positively correlated with FM% in G/G (R(2)=0.397, P<0.001) and was negatively correlated in C/C (R(2)=0.459, P=0.002). No significant correlation was observed in G/C genotype (R(2)=0.041, P=0.173). In conclusion our study confirms that, at least in Italian Caucasian females, the FM% is a major determinant of an increase in IL-6 production and insulin resistance. -174 G/C IL-6 promoter polymorphism represents a marker which could help to identify, time in advance, "vulnerable" individuals at risk of age and obesity related diseases.

Normal Weight Obese syndrome: role of single nucleotide polymorphism of IL-1 5Ralpha and MTHFR 677C-->T genes in the relationship between body composition and resting metabolic rate.

We have identified a subset of metabolically obese, but normal weight individuals, with potentially increased risks of developing the metabolic syndrome, despite their normal body mass index. We determined the relationship among body fat distribution, resting metabolic rate (RMR), total body water amount (%TBW), selected gene polymorphism on interleukin-15 receptor-alpha (IL-15Ralpha) and methylenetetrahydrofolate reductase 677C-->T (MTHFR 677C-->T), to distinguish normal weight obese (NWO) from nonobese with a normal metabolic profile and obese individuals. We analysed anthropometric variables, body composition by Dual energy X-ray Absorptiometry (DXA), RMR by indirect calorimetry, %TBW by bioimpedence analysis (BIA), MTHFR 677C-->T and IL-15Ralpha genotypes of 128 clinically healthy Caucasian individuals. We compared a group of female, defined as NWO and characterised by a BMI < or = 25 kg/m(2) and FM > or = 30% with groups of others female, and males, represented by nonobese with a BMI < or = 25 kg/m(2) and FM < or = 30%, and preobese-obese individuals with BMI > or = 25 kg/m(2) and %FM > or = 30%; none of the males was classified as NWO. Significant correlations were found among body fat mass distribution, metabolic variables, percentage of total body water distribution and selected genetic variations. The variables that contributed significantly to the separation of classes were body tissue (Tissue), %TBW, RMR, the volumes of both oxygen (VO2) and carbon dioxide (VCO2). The distribution of MTHFR 677C-->T and IL-15 genotypes was significantly different between classes. Our data highlight that NWO individuals showed a significant relationship between the decrease in the basal metabolism (RMR), body fat mass increasing and total water amount. Possession of wild type homozygotes genotypes regarding IL-15Ralpha cytokine and 677C-->T MTHFR enzyme characterised NWO individuals.

Body composition analyses in normal weight obese women.

The purpose of this study was to identify new indexes of body composition that characterize the normal weight obese (NWO) women. We measured body composition by dual energy x-ray absorptiometry (DXA) and resting metabolic rate (RMR) by indirect calorimetry in a cohort of seventy-five healthy Italian women, subdivided into three groups (nonobese/controls, NWO, preobese-obese women). Despite a normal body mass index (BMI), the NWO women have a higher body fat mass percentage (FAT %) (38.99 +/- 6.03) associated to a significant (p = 0.02) lower amount of lean mass of legs (12.24 +/- 1.31) and lean mass of left leg (6.07 +/- 0.64) with respect to the control group. The NWO group showed a significant (p = 0.043) lower RMR (1201.25 +/- 349.02) in comparison with nonobese and preobese-obese women. To classify NWO individuals among general population, we identified three significant body composition indexes: abdominal index, leg index and trunk index. The NWO women showed significant increased value in the three indexes (p < 0.001). Our results suggest that, despite a normal BMI, the NWO women displayed a cluster of anthropometric characteristics (body fat mass percentage, leg indexes) not different to obese women ones. An appropriate diet-therapy and physical activity may be protecting NWO individuals from diabetes and cardiovascular diseases associated to preobese-obese women.

The immunosuppressive cytokines influence the fetal survival in patients with pregnancy-induced hypertension.

PROBLEM: The present study examines the hypothesis that the elevated levels of transforming growth factor (TGF)-beta1 and interleukin (IL)-10 would be protective for the fetus survival during pregnancy-induced hypertension (PIH). Moreover, we evaluate the IL-12 and IL-15 serum concentrations and their relationships with PIH. METHOD OF STUDY: Serum samples were obtained before the onset of labor from control and PIH groups. Cytokine concentrations were determined by Enzyme-Linked Immunoadsorbent Assay. RESULTS: Our data show that PIH women have significantly higher TGF-beta1 and IL-10 concentrations with respect to control groups (P = 0.0001). Similarly, macrophages from the PIH placentas produce in vitro more elevated TGF-beta1 and IL-10 levels compared to normal pregnant ones (P = 0.02), also in the absence of LPS stimulation. IL-12 and IL-15 serum concentrations were not detectable in all pregnant groups. CONCLUSION: We have found that PIH women have elevated concentrations of anti-inflammatory/immunosuppressive cytokines, suggesting their important role in fetal allograft protection during the normal and pathological pregnancy.

Susceptibility to influenza A virus infection in mice immunosuppressed with cyclophosphamide.

It is known that immunocompromised hosts show an enhanced susceptibility to microbial infections. Among these, viral infections represent a particular problem because of the lack of really efficient antiviral drugs. In the present report we have studied the effect of pharmacological immunosuppression with cyclophosphamide (CY) in virus infection in vivo, using Balb/c mice infected with influenza A virus (PR8). At the dose of 0.1 hemagglutinating units of viral inoculum, intranasal administration of PR8 virus caused the death of 50 to 60% of the animals within a period of 3-10 days. A single injection of CY (200 mg/kg) significantly increased mouse mortality to 90%, when PR8 virus challenge was performed 4 days after chemotherapy pretreatment. When the PR8 virus infection was performed at different times after CY-treatment, a similar appreciable effect was not observed. Severe alterations of some immunological parameters such as NK activity and analysis of lymphoid spleen cell subsets were related to the increased susceptibility to virus infection.

Immunofluorescence study of thymuses of mice given Friend leukemia virus: conventional vs monoclonal antibodies.

In the course of a study of the early effects of Friend Leukemia Virus (FLV) infection in thymus structure and function, evidence of early localization of infectious FLV in the thymic type I and type II epithelio-reticular cells of susceptible mice was obtained. Such evidence was based upon bio-assay, ultrastructural and immunofluorescence observations. As for the latter, conventional monospecific sera against FLV p30 and gp70 antigens as well as two distinct monoclonal antibodies recognizing FLV gp70 epitopes were employed. Both monoclonal antibodies stained with a granular pattern the cytoplasm of type I and II epithelio-reticular cells from susceptible mice injected with live FLV. On the contrary, conventional monospecific sera diffusely stained the cytoplasm of all epithelio-reticular cells of the thymus, independently of mice inoculation with and susceptibility to virus, possibly recognizing tissue-associated normal mouse antigens and/or cross-reacting antigens of other ecotropic viruses.

[Effects of an antiserum for epithelial-reticular cells of the thymus on T-dependent immune response]. / Effetti di un siero anti cellule epitelio-reticolari del timo sulla risposta immunitaria T-depedente.

Relations between thymic factors and Prostaglandins (PG) were studied. We investigated on the effects of different incubation times with Thymosin Fraction 5 and Indomethacin on the release by spleen cells from normal or adult thymectomized mice. Prostaglandins were measured by radioimmunoassay. Thymosin induces an increase in PGE2 release on spleen cells obtained from thymectomized mice; the same effect was not observed on spleen cells obtained from normal mice.

[Release of prostaglandins by spleen cells in the mouse after incubation with thymosin]. / Rilascio di prostaglandine da parte di cellule spleniche di topo dopo incubazione con timosina.

The effects of i.p. administration in mice of a rabbit antiserum specific for thymic epithelial cells on T-dependent cellular immune response has been studied. As measure of T-dependent cellular immune response were taken: 1) a delayed type hypersensitivity test based on the swelling of footpad following SRBC injection in immunized mice; 2) a graft-versus-host assay valuated by splenomegaly induced in newborn mice after donors mice spleen cells i.p. injection. Both assays showed a significant reduction of cellular T-dependent immune response. The cinetic of this effect is in accord with ultrastructural changes in mice thymus, following the same treatment, previously observed.

[Relation between thymosin fraction 5, prostaglandin release and Thy-1 antigen appearance in mice lymphocytes]. / Correlazione tra timosina Fr 5, rilascio di prostaglandine e comparsa dell'antigene Thy-1 in linfociti di topo.

Incubation with Thymosin Fraction 5 induces a dose-dependent release of PGE2 by lymphocytes obtained from adult thymectomized mice; Indomethacin inhibits this effect. The same result was not observed in lymphocytes obtained from normal mice. PGE2 release is correlated with Thy-1 appearance on Thy-1 negative lymphocytes, after incubation with Thymosin, valutated with Bach's rosette inhibition test.

Effects of in vivo Friend leukemia virus infection on levels of serum thymic factors and on selected T-cell functions in mice.

The levels of serum thymic factor(s) (STF), of Thy-1.2 positivity of splenocytes [as measured by their azathioprine (AZ) sensitivity], and of Thy-1.2-positive "spontaneous" spleen rosette-forming cells (SSRFCs), as well as the presence of infectious virus in the thymus, were assessed as a function of time after virus inoculation in susceptible DBA/2, partially resistant BALB/c, and fully resistant C57BL/6 mice given the polycythemia- or anemia-inducing strain of Friend leukemia virus (FLV-P and FLV-A, respectively). As early as Days 2 to 3, the levels of STF and of AZ sensitivity of splenocytes were profoundly decreased in DBA/2 mice, and, to a lesser extent, in BALB/c mice given FLV-P; however, SSRFCs/spleen were increased in both mouse strains. Conclusive evidence of infectious FLV-P was obtained in the thymuses of DBA/2 mice soon after infection. In mice of the same strains infected with FLV-A, STF levels were similarly decreased, but AZ sensitivity of splenocytes was unaffected, and SSRFCs were decreased. Evidence of early FLV-A infection in the thymus of DBA/2 mice was likewise obtained. In C57BL/6 mice given FLV-A, STF levels, AZ sensitivity of splenocytes, and SSRFC showed changes similar to, but of lower magnitude than, those in BALB/c mice. On the other hand, in C57BL/6 mice given FLV-P, the decrease in STF and AZ sensitivity was almost as pronounced as in susceptible DBA/2 mice in the face of complete absence of infectious virus or viral markers in the thymuses. The observed changes are ascribed to virus infection in view of the following: (a) good temporal correlation between these changes and virus infection; (b) absence of any change in mice given heat-inactivated viruses or spleen homogenate of normal DBA/2 mouse spleen; (c) overall good correlation between mouse genotype and genetic (Fv-1 and Fv-2) restrictions of virus infection on one hand and the magnitude of the observed changes on the other. In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex. All changes described so far were transient, since they were not detectable beyond 42 days after virus inoculation in overtly leukemic animals. The observed derangements of thymus-derived immune functions may play an important cofactor role during the onset of leukemia in mice genetically permissive to Friend leukemia virus replication and transformation, but they do not seem relevant to the maintenance of leukemia.

[Incidence, type and significance of anti-myocardial autoantibodies in patients undergoing cardiac surgery]. / Incidenza, tipoe significato degli autoanticorpi anti-miocardio in pazienti sottoposti a trattamento cardiochirurgico.

The incidence of anti-myocardial autoantibodies was investigated in 62 patients suffering from congenital or acquired cardiopathy prior to and 1, 10 and 20 days after cardiac surgery. Anti-myocardial autoantibodies were present in about 23.7 per cent of patients even before surgery, practically doubled one day after intervention, reached their peak (60-70 per cent) at 10 days from surgery and began to diminish at 20 days. At all times and incidence was higher in patients with acquired cardiopathy than in those with congenital heart diseases. In the large majority of cases, the autoantibodies were of the IgG class, of the striational type and in low titers. The relevance of anti-myocardial autoantibodies in the pathogenesis of cardiac lesions and the possible causes of the reversibility of the autoimmune phenomenon are discussed.

[Preliminary study on the effects induced by an anemic strain of Friend leukemia virus in DBA/2 mice]. / Studio preliminare sugli effetti indotti dal ceppo anemico del virus della leucemia di Friend in topi DBA/2.

Serum thymic factor (STF) and azathioprine (AZ) inhibition test were assayed in sera and spleen cells from DBA/2 and BALB/c mice, inoculated with the anemic strain of Friend leukemia virus. The observed decrease of STF levels appears to be related to the LLV (Lymphatic Leukemia Virus) component of FLV-A.