The main critical issues of the gym environment in an Italian city.

BACKGROUND: The lack of a consistent national regulation regarding gym facilities, combined with the growth and transformation of the world of fitness, has led to an uncontrolled situation, where, especially in metropolitan areas, low cost gyms are continuously popping up, often not respecting the structural and hygienic requirements. AIM OF THE STUDY: Objective of this study is to evaluate the results of a monitoring programme about the gym environment, to highlight the main critical issues. METHODS: In 2018 a randomized sample of 90 gyms was inspected in Milan, using a checklist with three sections of inquiry and the resulting data were analysed through a series of multivariate regression models. RESULTS: As per the various aspects analysed, many outcomes with low scores concerned franchised gyms, which have shown to be unsatisfactory in many respects; in addition, the lack of L. pneumophila risk containment procedures has been observed in the facilities without a swimming pool, compared to those with it. CONCLUSIONS: The study results offer a clear picture of the gym environment, identifying many inadequacies for different hygienic and safety aspects; therefore, it has been possible to understand which issues need particular attention in order normalize the situation, which should be checked by future investigative steps.

Innate and adaptive immune responses to the major Parietaria allergen Par j 1 in healthy subjects.

In this study we wanted to analyse the pattern of the immune response to the Parietaria major allergen Par j 1 in freshly purified peripheral blood mononuclear cell (PBMC) from healthy subjects. We observed that Par j 1 was capable of inducing IFN-γ production by CD3⁻ and CD16⁺/CD56⁺ cells exclusively in healthy individuals. Furthermore, a multiparametric analysis allowed us a better definition of two IFN-γ-Par j 1 specific populations (IFN-γ(dim) and IFN-γ(high)) characterized by the presence of different proportions of NKT and NK cells. We also identified the concomitant presence of a subset of IL-10⁺ NK cells. Moreover, CFSE staining showed that the Par j 1 preferentially induced the proliferation of CD3⁻/CD56⁺/CD335⁺ cells. Finally, a subset of CD4⁺/CD25⁺/FoxP3⁺/IL-10⁻ T cells was identified. The result of this pilot study suggest that during a tolerogenic response, the major allergen of the Parietaria pollen works as an activator of both the innate and the adaptive human immune system.

Measurement of inflammatory mediators of mast cells and eosinophils in native nasal lavage fluid in nasal polyposis.

BACKGROUND: Nasal polyposis (NP) often coexists with asthma, rhinitis and sinusitis. Polyp histology typically shows chronic, eosinophilic inflammation. The inflammatory cell infiltrate generally includes eosinophils, lymphocytes, plasma cells and mast cells. OBJECTIVE: To gain insight into the natural history of NP, we analysed mediator levels and leukocyte values in nasal fluids and eosinophil cationic protein (ECP), total IgE levels and eosinophils in the blood in several groups of both allergic and non-allergic patients with nasal polyps and in patients with allergic rhinitis (AR). METHODS: Thirty-two patients with nasal polyps entered the study. As a control group, we studied 55 patients with AR, i.e. 20 patients with seasonal AR to grass pollen, 24 with AR sensitive to Parietaria and 11 with AR sensitive to house dust mite (HDM). Eighteen patients with nasal polyps were also allergic patients (8 were sensitive to Parietaria and 10 were sensitive to HDM), whereas 14 were non-allergic patients. Tryptase and histamine values were assayed in nasal fluids, whereas total IgE was determined in serum. ECP values were assayed both in nasal fluids and serum. Eosinophils were quantified both in the blood and nasal fluids. RESULTS: Tryptase levels were significantly higher in the nasal lavages from patients with NP than in those from patients without NP (4.7 vs. 3.5 U/l, p < 0.001) and correlated with symptom scores (r(s) = 0.42, p < 0.0001). The median levels of histamine in nasal fluids from patients with NP were also significantly higher than those observed in patients without NP (50.0 vs. 21.3 ng/ml, p < 0.001), but did not correlate with symptom scores. Finally, the median levels of ECP in nasal fluids from patients with NP were significantly higher than those observed in patients without NP (38.1 vs. 16.1 ng/ml, p < 0.001) and correlated with symptom scores (r(s) = 0.38, p < 0.001). Analysis of variance showed that, among the variables studied, the presence of nasal polyps was the factor responsible for the higher levels of tryptase, histamine and ECP in nasal fluids. With regard to leukocyte counts in nasal fluids, no significant differences were observed between rhinitis patients with NP and those without NP. With regard to serum ECP and serum total IgE, no significant differences were detected between the two groups under study. Blood eosinophil levels in patients with NP were significantly higher than those observed in patients without NP (5.8 vs. 5.6, p = 0.002). Analysis of variance showed that both the presence of nasal polyps and the type of sensitisation were important. Considering the total symptom scores, no significant differences were observed between rhinitis patients with NP and those without NP. CONCLUSIONS: The present findings are consistent with the view that chronic eosinophil mucosal inflammatory disease in NP involves a self-sustaining mechanism, i.e. local release of inflammatory mediators, independent of allergen stimulation of nasal mucosa. Increased release of inflammatory mediators contributes to the development of nasal polyps, determining oedema and an increased recruitment of inflammatory cells. Besides eosinophils, mast cells also play a key role in this process.

A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity.

The 8.1 ancestral haplotype (AH) is a common Caucasoid haplotype carried by most people who type for HLA-B8,DR3. It seems unique in its association with a wide range of immunopathologic diseases. Healthy subjects bearing this haplotype demonstrate several alterations of immune response. This article will focus on the identification of the mechanism(s) of disease susceptibility of 8.1 AH. In 13 carriers of 8.1 AH, and 43 negative patients, enzyme immune assays serum levels of tumor necrosis factor (TNF)-alpha, soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), cortisol, and interleukin(IL)-10 were determined. In addition, quantification of cytokine produced in vitro after mitogen stimulation was studied, and all subjects were genotyped for alleles at -592, -819, and -1082 nucleotides of IL-10 gene 5' flanking region, which is known to control IL-10 production. Results revealed that 8.1 AH is associated with a high in vivo and in vitro production of TNF-alpha, which in turn seems responsible for increased serum levels of sELAM-1, cortisol, and IL-10. On the contrary, in vitro production of IL-10 is not increased in these patients and there are no differences in allele promoter frequencies between the two groups that might explain the differences in IL-10 serum values. Thus, serum values seem to be the result of the effects of increased serum levels of TNF-alpha and cortisol. In conclusion, the increased spontaneous release of TNF-alpha, which modifies a certain number of immunologic parameters, may be the most characterizing feature of 8.1 AH. The consequent modification of the immunologic scenario might be involved in the predisposition to the impressive number of diseases and the changes in immune response observed in the patients studied.

In vitro treatment with interleukin-2 normalizes type-1 cytokine production by lymphocytes from elderly.

The term immunosenescence is taken to mean the deterioration of immune function seen in elderly, which is manifested in increased susceptibility to infectious diseases, neoplasias, and autoimmune diseases. It is only recently that we have begun to understand the cellular and molecular changes involved. Of special interest in this regard are observations of a decline in synthesis of Type-1 cytokines which predisposes to diminished cell mediated immunity. We have evaluated the production of type 1 cytokines in old and young donors either in presence or in absence of recombinant interleukin-2 (rIL-2). Lymphocytes were stimulated with plastic bound anti-CD3 and after 48 h the supernatants were harvested and stored at -70 degrees C until assay. Type 1 cytokine, i.e. IL-12 and interferon-gamma (IFN-gamma) production by anti-CD3 stimulated lymphocytes from old subjects was significantly reduced when compared to that from young ones. This impaired production was reversed by adding rIL-2 in the culture medium. In previous studies on aged subjects, we have been able to demonstrate that in vitro treatment with rIL-2 completely restores proliferative responses and partially rescues the increased apoptosis of T cell cultures. Present and previous results suggest that rIL-2 completely restores Type 1 responses by overcoming the well known costimulation deficit of aged lymphocytes.

Comparison of the effects of fluticasone propionate, aqueous nasal spray and levocabastine on inflammatory cells in nasal lavage and clinical activity during the pollen season in seasonal rhinitics.

BACKGROUND: Treatment options for allergic rhinitis include antihistamines, decongestants, anticholinergics, cromolyn sodium and corticosteroids. As the nose is a small organ, comprising less than 1% of total body mass and surface area, it seems logical to confine treatment of rhinitis to the diseased organ. OBJECTIVE: To evaluate the effects of therapy with intranasal fluticasone propionate (FP), both on subjective symptoms and pathophysiological mechanisms, in rhinitis patients during pollen season when the patients were symptomatic. METHODS: We used a double-blind, placebo (PLA)-controlled, randomized, double dummy, parallel group study of the effect of 6 weeks treatment. The double-blind comparison was made between the following three treatments: FP aqueous nasal spray, 200 microg taken once daily, levocabastine (LEV) nasal spray, 200 microg taken twice daily and PLA nasal spray. Clinical evaluation and the levels of cells and mediators in nasal washing were performed before and after treatments. Twenty-four patients (11 men and 13 women, aged 17-50 years, mean age 30.1 +/- 8.5) with strictly seasonal allergic rhinitis to Parietaria entered the study. Clinical evaluation and the levels of inflammatory cells (eosinophils and activated eosinophils, i.e. EG2+) and their mediators (tryptase, eosinophil cationic protein, eosinophil protein X and neutrophil myeloperoxidase) in nasal-lavage were performed before and after treatments. RESULTS: Treatment with FP significantly increased, with respect to placebo, the percentage of days without sneezing (P < 0. 001), nasal blockage (P < 0.001), rhinorrhea (P < 0.001), nasal itching (P < 0.001). Furthermore, treatment with FP showed additional benefits with respect to LEV. The percentage of days without nasal blockage was significantly higher in the FP group that in the placebo group (P = 0.018). The same applied to rhinorrhea (P = 0.009). The percentages of days without sneezing and itching were instead not significantly different between the two groups. As expected, no significant differences were observed in baseline medians of the rhinitis symptom scores as well as in mean values of all mediators and eosinophils in nasal lavages of the various groups under study. After treatment the mean of subjective symptoms as well as all values in nasal lavage level fell significantly only in the FP group, whereas no significant changes were observed either in LEV or PLA groups. Accordingly, significant differences were observed at the end of the treatments between the values of fluticasone group vs LEV and PLA group values. Significant correlations between these values and symptom scores were found, according with literature data suggesting a pathogenetic role for these mediators and eosinophils in rhinitis. CONCLUSION: FP (200 microg once daily) affords a significant degree of improvement in rhinitis control during pollen season, as measured by subjective and objective parameters, compared with LEV (200 microg twice daily) and PLA. The therapeutic benefits of intranasal FP are reflected in, and may be caused by, the decrease in nasal inflammatory cells.

Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes.

Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3-11 years, 15-39 years, 41-60 years, 61-74 years, 75-84 years, 85-102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared with the oldest old groups. In the cord-blood group, the absolute number of all the lymphocyte subsets was enhanced, but in the oldest group, an increase of CD16+ lymphocytes was observed, whereas CD19+ lymphocytes, which progressively decrease with age, continue to decrease further in the very old. The data show that the expression of CD95 increases until age 74 years, whereas in the oldest old it tends to decrease again. The trend of CD95 expression seems to be related to the change of expression of CD95 on CD4+ lymphocytes, because the CD8+/CD95+ population rose steadily throughout the entire age range. The evaluation of CD95+/CD45R0+ lymphocytes shows similar results to those observed analyzing CD95 on total lymphocytes. Furthermore, a constant increase of CD95+/CD28+ and a related decline of CD28+ lymphocytes was observed in all age groups. These data suggest that the expression of CD95 on the different subsets of lymphocytes can be considered a good marker for studies of immunosenescence, because it may be predictive of successful aging, and can partially explain the change in lymphocytes subsets in elderly.

Granulocyte and natural killer activity in the elderly.

The deterioration of the immune system in ageing, 'immunosenescence', is thought to contribute to increased morbidity and mortality from infections and possibly autoimmune diseases and cancer. The most profound changes involve effector and immunoregulatory T-cell functions. Immunosenescence appears also to be related to changes in non specific immunity as well. In the present study we have assessed superoxide production, chemotaxis and the expression of the apoptosis-related molecule APO1/Fas (CD95) on neutrophils (PMN) from young and old subjects. Furthermore, we have measured the basal natural killer (NK) activity of young and elderly subjects and we have compared the number of CD16+ cells found in these two groups. We observed a significant decrease age-related both of formation of O2- and chemotaxis whereas no significant correlation between age and the expression of CD95 on granulocyte membrane was demonstrated, suggesting that an increase age-related of CD95-linked apoptosis of PMN should be not an important determinant in the decreased PMN function. We also observed a significant correlation between age and NK activity. The decreased NK cell function was not due to a decreased number of NK cells in effector cell preparations since the number of CD16+ cells was significantly increased in old subjects. In conclusion, our results show that in the elderly there is also a deficit of the aspecific immunity that might play a role in the pathogenic mechanisms of the immunosenescence.

Apoptosis and ageing.

Stimulation of T cells from aged individuals leads to different kinds and/or size of responses if compared with the responses of T cells obtained from young individuals. In fact elderly is associated with a progressive decline of immune response besides an increasing incidence of autoimmune phenomena. These differences might be the result of modified cellular mechanisms controlling the immune system in the course of ageing. The apoptotic deletion of activated T cells has been proposed as the key mechanism to maintain T cell homeostasis, and in this respect CD95 (Fas antigen) seems to play a major role in this course of events. In this study we show that just collected lymphocytes from old subjects displayed an increased expression of the apoptosis molecule CD95. The expression of CD95 and the spontaneous apoptosis showed the same trend. In fact the percentage of apoptotic cells in blood collected from old subjects was enhanced too. The lymphocyte subpopulation analysis by flow cytometry did not show significant changes in T subset percentages between old and young subjects. Moreover mononuclear cells obtained from aged individuals underwent apoptosis in culture in response to a single stimulation with mitogen or anti-CD3, more than mononuclear cells from young controls. To gain insight into mechanisms of this increased apoptosis, experiments were performed to evaluate the behaviors of lymphocytes from old and young donors in respect of interleukin-2 (IL-2) rescue from apoptosis. Results show that IL-2 rescued only a little fraction of cells of old donors from apoptosis when activated by anti-CD3 and that this effect was not related to a different expression of CD95. Thus, during the course of ageing the different regulation of T cell homeostasis might be also explained by the modified proneness of lymphocytes to undergo apoptosis. The contemporaneous demonstration of a reduced Ca2+ influx in lymphoid cells of these subjects allows to suppose that multiple defects play a role in the pathogenesis of immunosenescence.

Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly.

Defects involving cellular expression of activation molecules, cell mediated immune response and natural killer (NK) activity are commonly observed in the elderly. Herein, data are reported on the evaluation of IL-12 production by old subjects. IL-12 is, actually, considered the key molecule for the induction of a T helper 1 (Th1) -type and NK response. IL-12 production from old subjects peripheral blood mononuclear cells (PBMNC) was evaluated using T-independent (bacterial lipopolysaccharide, LPS) or -dependent (phytoemagglutinin, PHA; immobilized anti-CD3 monoclonal antibodies, anti-CD3) mitogens. The IL-12 production after LPS stimulation was not reduced in cultures from old subjects when compared to that from young ones. On the contrary, IL-12 production by PHA or anti-CD3 stimulated PBMNC from old subjects was decreased. Furthermore, we have demonstrated a reduced CD40 and CD40 ligand (CD40L) expression on PBMNC from old subjects. This finding fits very well with the reduced cytokine production observed in the T-dependent stimulation systems, being the CD40-CD40L interaction mandatory for an efficient IL-12 production. All together, these results seem to suggest that defects in cell expression of activation molecules can affect the IL-12 secretion and in consequence other Th1-type cytokines.

Gluten stimulation induces an in vitro expansion of peripheral blood T gamma delta cells from HLA-DQ2-positive subjects of families of patients with celiac disease.

The intestinal gluten sensitivity formally known as celiac disease (CD) is characterized by an evident involvement of local immune response and it is associated with the expression of HLA-DQ2 allele. The major role in the disease seems to be played by the T lymphocyte population bearing gamma delta T cell receptor (T gamma delta cells) which are increased both in peripheral blood and intestinal mucosae of celiac patients. In this paper data on the effects of in vitro gluten stimulation on lymphocytes expressing the T gamma delta phenotype are reported. Gluten seems to be able to induce the expansion of the T gamma delta cell population both in CD patients and their HLA-DQ2-positive asymptomatic relatives, in spite of the absence of clinical evidence of the disease. In addition, the evaluation of gluten-induced cytokine production shows that interleukin-4 could be implied in the early phases of pathogenesis of CD.

Biological basis of the HLA-B8,DR3-associated progression of acquired immune deficiency syndrome.

The factors influencing the evolution of human immunodeficiency virus (HIV) infection are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of the disease by affecting the immune response to HIV. The role of the host human leukocyte antigen (HLA) genotype in the regulation of susceptibility to HIV infection and expression has been studied extensively in different major risk groups. Certain HLA alleles and haplotypes, being associated with aberrant immune responses independently from HIV infection, have been reported to facilitate the rapid progression of disorders related to HIV infection. Particularly, the association of rapid acquired immunodeficiency syndrome (AIDS) progression with genes from the HLA-B8,DR3 haplotype has been reported by different research groups. It is well known that this haplotype is associated in all Caucasian populations with a wide variety of diseases with autoimmune features and in healthy subjects with a number of immune system dysfunctions, as a reduced production of T helper (Th)1 type cytokine. HIV infection may act on this genetic background triggering immunopathogenetic mechanisms leading to AIDS with a dominant Th2 profile as a common feature.

Identification of novel mRNA transcripts of the nm23-M1 gene that are modulated during mouse embryo development and are differently expressed in adult murine tissues.

The nm23-M1, a putative metastasis-suppressor gene, and its homologs are involved in development and differentiation. We have shown previously that in vitro neuronal cell proliferation and differentiation can be modulated by nm23-M1 expression levels. In the present study, by the yeast two-hybrid system, we have shown that, at the onset of mouse tissue differentiation, the Nm23-M1 protein forms either homodimers, or heterodimers with Nm23-M2. Furthermore, we have isolated two cDNA variants of the nm23-M1 gene in the 3'-untranslated region (UTR). The two variants related to novel mRNA transcripts that are modulated in mouse embryo and are differently expressed in adult murine tissues.

HLA-B8,DR3 haplotype affects lymphocyte blood levels.

The number of lymphocytes in the blood is constant, pointing to an effective control of circulating lymphocyte values. The mechanisms of this regulation are uncertain, although it is likely that the number of blood lymphocytes is conditioned by hormones, homing factors and cytokines whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility complex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present study, to inquire into the mechanisms of this lymphocyte decreased number, we have performed an analysis of blood subset values in these subjects. When the absolute values of lymphocytes were analysed according to HLA phenotype, HLA-B8,DR3 positive subjects (N = 26) displayed significantly lower values as compared to HLA-B8,DR3 negative ones (N = 282). The analysis of lymphocyte subpopulations performed by flow cytometry in 72 subjects did not show significant changes in lymphocyte subset percentages between HLA-B8,DR3 positive subjects and negative ones. Thus, the decrease of circulating lymphocytes seems to be due to a reduction of cell number affecting all lymphocyte subsets rather than a single cell subpopulation. The analysis of in vitro spontaneous apoptosis performed by flow cytometry in a smaller sample of subjects showed a significant increase of spontaneous apoptosis in lymphocytes from HLA-B8,DR3 positive individuals suggesting a possible explanation for the deviation from normal lymphocyte count observed in these subjects. However it is intriguing that a decreased number of blood lymphocytes can be observed in healthy HLA-B8,DR3 positive subjects but also in autoimmune diseases linked to this haplotype like systemic lupus erythematosus and insulin-dependent diabetes. Furthermore, in our opinion, this finding is to be kept in mind in evaluating hematological parameters in healthy subjects.

gamma delta cells involved in contact sensitivity preferentially rearrange the Vgamma3 region and require interleukin-7.

Ptak and Askenase showed that both alphabeta and gammadelta cells are required for transfer of contact sensitivity (CS). This study confirms that day 4 immune cells depleted of gammadelta cells fail to transfer CS to trinitrochlorobenzene (TNP-Cl) systemically and demonstrates that administration of anti-gammadelta monoclonal antibodies (mAb) in vivo abolishes the CS reaction. Moreover, gammadelta cells accumulate at the antigen challenge site: these cells have the unusual phenotype CD8alpha+, CD8beta-, IL-4 R+ which we suggest is due to their state of activation. Following immunization with contact sensitizer on the skin, the absolute number of gammadelta cells increases in the regional lymph nodes with a peak at 4 days. Of the gammadelta cells, 80 %, both in the lymph nodes of TNP-Cl-immune mice and accumulating at the antigen challenge site are Vgamma3+. The gammadelta cells expressing Vgamma3, which is characteristic of dendritic epithelial T cells (DETC), obtained 4 days after sensitization, proliferate in response to interleukin (IL)-7, but only poorly to IL-2 and IL-4. They also respond to concanavalin A and immobilized anti-gammadelta mAb, but not to haptens or heat-shocked syngeneic spleen cells. Furthermore, injection of mice with mAb to IL-7 inhibits accumulation of Vgamma3+ cells both in the lymph nodes after skin sensitization and at the antigen-challenge site. Altogether, these results strongly support the view that DETC are related to, or the original source of, the gammadelta cells found in the lymph node after skin sensitization and at the site of challenge, and that IL-7 is implicated in these phenomena.

Plasma levels of tumor necrosis factor-alpha and interferon-gamma in Sicilian children with Mediterranean spotted fever.

The plasma levels of tumor necrosis factor-alpha and interferon-gamma were measured in 53 consecutive children with serologically confirmed Mediterranean spotted fever and were found to be increased during the acute phase compared with the convalescent phase (tumor necrosis factor-alpha mean 32.17 vs. 4.12 pg/ml, P < 0.0001; interferon-gamma mean 84.17 vs. 2.65 pg/ml, P = 0.0006). Plasma levels of both cytokines were higher in patients with a typical exanthema rather than those with a very mild or no exanthema; tumor necrosis factor-alpha levels were significantly lower in the latter (tumor necrosis factor-alpha 32.17 vs. 9.85 pg/ml, P < 0.0001; interferon-gamma 84.17 vs. 38.14 pg/ml, P = 0.35). Tumor necrosis factor-alpha and interferon-gamma may be harmful or beneficial to the infected host, depending upon the amounts produced and whether they are circulating or confined locally to the site of inflammation.

Modification of cytokine patterns in subjects bearing the HLA-B8,DR3 phenotype: implications for autoimmunity.

The factors influencing the pathogenesis of autoimmune disease are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of these diseases. The role of the host's major histocompatibility complex (MHC) genotype in the regulation of susceptibility to autoimmune diseases has been extensively studied in different populations, and certain HLA (the human MHC) alleles and haplotypes have been reported to be associated with several autoimmune diseases. In particular, the association with genes from the HLA-B8,DR3 haplotype has been reported by different research groups. This haplotype is associated in all Caucasian populations with a wide variety of diseases with autoimmune features, and in healthy subjects it is associated with a number of immune system dysfunctions. Mainly, peripheral blood mononuclear cells from HLA-B8,DR3-positive and -negative individuals differ in their ability to produce interleukin (IL)-2, IL-5, IL-12 and interferon-gamma upon stimulation with the mitogen phytohaemoagglutinin (PHA), while producing similar amounts of IL4, IL-6 and IL-10. Furthermore, in HLA-B8,DR3-positive subjects tumor necrosis factor alpha secretion is increased both with and without PHA stimulation. Accurate control of the functional repertoire of an immune response is a critical parameter in the response to infections as well as in immunopathology. MHC control of the class of the immune response at the level of cytokine production is a sophisticated way in which this occurs. This control might be involved in adaptive immune responses to infections as well as in immunopathology.

nm23 influences proliferation and differentiation of PC12 cells in response to nerve growth factor.

The nm23 genes codify nucleoside diphosphate kinases, which have been shown to be involved in the regulation of microtubule dynamics. We have demonstrated previously that the association between the Nm23-M1 protein and cytoskeletal beta-tubulin correlates with cell differentiation. It is known that microtubules and microtubule-associated proteins are fundamental elements regulating neuronal differentiation. In the present study, we have investigated the ability of nm23 to influence nerve growth factor-induced PC12 cell differentiation. To this end, we have altered PC12 intracellular levels of nm23-M1 by means of sense and antisense transfections. In the presence of nerve growth factor, overexpression of nm23 delays cell cycle transition, rapidly induces neurite outgrowth, and increases the expression of neurofilament and microtubule proteins. On the contrary, down-regulation of nm23 enhances cell proliferation and inhibits neuronal differentiation. These findings indicate that neuronal cell proliferation and differentiation can be modulated by nm23 expression levels.

[An experimental in-vitro evaluation of membrane antigen expression and of interleukin production by monocytes exposed to magnetic resonance]. / Valutazione sperimentale in vitro dell'espressione di antigeni di membrana e della produzione di interleuchine da parte di linfomonociti esposti a Risonanza Magnetica.

The interactions of magnetic fields and radiofrequency with biological systems have been described by several authors. However, no definitive conclusions have been drawn yet as to the safety of the magnetic fields and radiofrequencies used in clinical examinations. The immune system is one of the most complex biological systems, in which a network of intracellular signals regulates the immune response. Interleukins are released by an activation process which involves, at least in part, intra- and/or extracellular calcium mobilization. The latter step can be influenced by the in vitro effect of this type of nonionizing radiations produced by an MR system on peripheral blood mononuclear cells. Our results show that the 2-hour exposure to magnetic fields (0.5 T) and radiofrequency caused an increase in the spontaneous release of IL2, IL4, IL10, TNF alpha and INF gamma, while the amount of the same cytokines induced by PHA stimulation was decreased. No differences were observed in the spontaneous or PHA-induced release of IL6 by exposure to magnetic fields (MRI). Furthermore, the expression of the CD 11b molecule was increased at the same time. These results may be useful for us to understand the interactions between magnetic fields and radiofrequencies and the immune system.