Carlo Lorenzo Cazzullo

Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease

In the pathogenesis of Alzheimer disease (AD), it has been proposed that the anti-inflammatory interleukins such as IL-10 regulate beta-amyloid-induced microglial inflammatory responses inhibiting the proinflammatory cytokine IL-6. Since the promoters of the IL-10 and IL-6 genes show single nucleotide polymorphisms (SNPs) (IL-10: -1082 G --> A; IL-6: -174 G --> C), we investigated these SNPs and cytokine production by peripheral blood mononuclear cells in 65 AD patients and 65 controls (HC). In AD there was a significant increase of the -1082A IL-10 allele (P=0.009) and a decrease of -1082GG genotype (P=0.019). The frequency of the GG IL-6 genotype in AD was lower and the C allele significantly higher (P <0.005). The co-occurrence of IL-10 A and IL-6 C alleles significantly raised the odds ratio (OR 11.2, confidence interval: CI 1.3-97.3; P <0.05) independently of apolipoprotein E4 (adjusted OR 10.3, CI 1-108; P <0.05). Only amyloid-stimulated IL-10 production differed between the groups (P=0.023). These results raise questions regarding the inflammatory theory in AD, pointing to a pivotal role of IL-10 and IL-6 and a selective alteration in this network.

CYTOKINES PRODUCTION IN CHRONIC SCHIZOPHRENIA PATIENTS WITH OR WITHOUT PARANOID BEHAVIOUR

1. Several immunological abnormalities have been found in schizophrenia but their significance still remains largely unknown. In this study the authors analyzed mitogen-stimulated interleukin (IL)-2, Interferon gamma (IFN)-gamma and IL-10 (type 2 cytokine) production in a sample of 37 chronic schizophrenic patients as compared with a sample of 40 age and sex-matched controls with the aim to evaluate whether patients belonging to different diagnostic subtypes (i.e. paranoid patients vs non paranoid patients) could be immunologically different from each other. 2. The findings indicate that paranoid patients produce less IL-10 than the others and thus, from an immunological viewpoint, they are more similar to healthy controls. 3. Furthermore, neuroleptic medications were observed to differently affect IL-2 production; this preliminary finding might stimulate further studies aiming to get a link between different drug profile of action both in terms of clinical and receptorial profile and different immunological effects.

Cytokine profiles in schizophrenic patients treated with risperidone: A 3-month follow-up study

An increasing body of evidence suggests a role for the immune system in the pathogenesis of schizophrenia. The information concerning the effects of antipsychotics on cytokine profiles are limited and often controversial in particular regarding novel antipsychotics. The authors first investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n = 12) and drug-naive (n = 3) schizophrenic patients and in healthy controls (n = 33) and then the modifications of cytokines values during a 3-month period of treatment with risperidone. In the baseline condition, the production of IL-2 and INF-gamma was significantly higher (P = .023 and .026, respectively) in patients than in controls. In the same patients, the use of risperidone was associated with augmented IL-10 (a suppressor of Type I cytokines) and decreased INF-gamma production. This modification suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in not currently treated schizophrenic patients.

Probing Memory and Executive Functions with Virtual Reality: Past and Present Studies

The technology of virtual reality (VR) has been used to develop interactive programs that simulate everyday life environments, where healthy subjects and patients with central nervous system dysfunctions are asked to carry out tasks that probe incidental memory and executive functions. The results of three studies support previous claims that VR-based tests overcome several limitations of traditional paper-and-pencil tests, are at least as sensitive to target cognitive impairments, while providing a richer range of opportunities for measuring behavior. Preliminary analyses also suggest that results of VR-based memory tests are replicable across laboratories and subjects samples and that the technology is well-accepted and tolerated by both healthy and impaired subjects.

Cytokine profiles in drug-naive schizophrenic patients

A large body of evidence concerning immunological abnormalities in schizophrenic patients seems to suggest a role of the immune system in the multifactorial pathogenesis of schizophrenia. We investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n=26) and drug-naive (n=7) schizophrenic patients and in healthy controls (n=33). Production of IL-2 and INF-gamma was significantly higher (respectively P=0.021 and P=0.001) in patients than in controls. These findings provide further evidence that immunological abnormalities are present in some schizophrenic patients.

Lymphocyte subsets in schizophrenic disorders: relationship with clinical, neuromorphological and treatment variables

Peripheral blood lymphocyte subsets and serum immunoglobulin levels were assessed in 42 patients and 37 healthy controls. 24 patients were free from neuroleptic medication and 15 had never been treated with neuroleptics. 31 patients had a diagnosis of schizophrenia (DSM-III criteria) and 11 a diagnosis of a disorder of the schizophrenic spectrum. As compared to healthy subjects, the drug naive schizophrenic patient group showed an increase of T suppressor lymphocytes, while the drug-treated schizophrenic group showed an increase of T helper lymphocytes. The drug-treated schizophrenic group differed from the drug naive one relative to a decrease of T suppressor lymphocytes. As compared to healthy subjects, the drug naive spectrum disorder patients showed an increase of absolute number of lymphocytes, while the drug treated spectrum group showed an increase of B lymphocytes. These findings did not correlate with any clinical or neuromorphological variables taken into account.

Increased levels of CD8+ and CD4 + 45RA + lymphocytes in schizophrenic patients

Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum immunoglobulins and C3 and C4 complement fractions were evaluated in 29 schizophrenic patients, 31 of their relatives and 20 healthy subjects. The patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3 months prior to the PB sample collection. When compared to healthy controls and their own relatives, the schizophrenic patients showed a lower level of CD4+ cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely, the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in schizophrenic patients in comparison to their relatives and controls, while the CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4 complement fraction levels among the three groups. The present data confirm the presence of immunological abnormalities in schizophrenic patients and suggest a possible role of environmental factors in the triggering of an autoimmune pathogenic mechanism.

The association between expressed emotion, illness severity and subjective burden of care in relatives of patients with schizophrenia. Findings from an Italian population

BackgroundAn appropriate understanding of the association between high-Expressed Emotion (EE) in family members of people with schizophrenia, patients’ and relatives’ correlates is needed to improve adaptation of psychoeducational interventions in diverse cultures. The aim of this study was to test the hypothesis that relatives designated as high EE would report higher subjective burden of care, and would be associated with objective variables that indicate greater illness severity i.e. number of previous hospitalizations and duration of illness.MethodsWe performed secondary analyses of baseline data from a randomized controlled trial conducted in Italy.ResultsHigh-EE relatives reported more subjective burden of care in disturbed behaviours and adverse effects areas, but did not perceive more deficits in social role performances. As regards illness severity characteristics, neither the number of previous hospital admissions nor the duration of illness was associated with high-EE. However, patients’ previous psychosocial functioning, as measured by educational attainments, seems to protect the relative from high-EE status.ConclusionThere is a need for cross-cultural comparisons of the subjective experience of distress and burden among high EE carers as a target for intervention, aimed at reducing family stress as much as improving patient outcomes.

Decrease of CD4+ CD45+ T-cells in chronic-progressive multiple sclerosis

SummaryCirculating lymphocyte subpopulations defined by anti-CD45 and other more common T-cell-specific monoclonal antibodies were analysed in 77 patients with multiple sclerosis and 38 healthy controls. A selective decrease of CD4+ CD45+ cell percentages and absolute numbers in chronic-progressive patients was found; in 13 out of 26 patients this subpopulation was less than 11% CD4+ CD45+ cells. Similarly, the whole CD45+ cell subset, as well as CD45+ cells expressed as percentages of CD4+ cells, were significantly reduced in chronic-progressive multiple sclerosis. CD4+ CD45+ cells, commonly termed “inducer of suppression” T-lymphocytes, did not correlate with percentages or numbers of CD8+ cells. It is concluded that suppressor inducer T-cells act on the CD8+ subset function rather than reducing CD8+ cell numbers. Since CD4+ CD45+ cells represent an early stage of lymphocyte maturation (naive T-cells), an under-representation of this subpopulation in active multiple sclerosis might reflect an increased conversion of naive cells into memory cells. This concept may be relevant for a better understanding of the disease pathogenesis.

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.