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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 127 records · Page 7Linked to original sources

Spontaneous adhesiveness of lipid-free myelin basic protein to immune cells as detected by a double labelling technique.

We have investigated whether immunocompetent cells have the capacity to interact directly with the myelin basic protein (MBP) of the central nervous system. To this end we have applied a double tagging system in order to study whether purified lipid-free MBP is able to bind to normal peripheral blood mononuclear cells (PBMC) without the need to purify the cells. Evaluation of MBP binding to PBMC was determined with biotinylated MBP and fluoresceinated avidin, and lymphocytes population was identified by the corresponding phycoerythrinated monoclonal antibody (MoAb). The contemporary use of MoAbs and avidin unambiguously showed that MBP is able to bind to both B and T lymphocytes. The biological significance of MBP adherence to immune cells still needs clarification.

Antibodies, Monoclonal↗

Effects of benzodiazepines on the immune system.

Benzodiazepines (BDZ) are psychotropic drugs largely used in patients with affective disorders. As far as their effects on the immune system are concerned, a few studies have been carried out until now. Diazepam is inhibitory in vitro for the phagocytic functions and the antibody synthesis, being its action mediated via specific receptors on immunocompetent cells. On the contrary, alprazolam results to be enhancing for the antibacterial activity exerted by normal human peripheral blood T lymphocytes in vitro. Taken together, these data point out the different role which BDZ play on the immune response.

Alprazolam↗

Alprazolam enhances the antibacterial activity exerted by normal human peripheral blood lymphocytes.

The effects of two benzodiazepines, diazepam and alprazolam, have been evaluated on the in vitro antibacterial activity exerted by human peripheral blood lymphocytes (PBL). Results demonstrate that diazepam has no influence on this PBL function, while alprazolam is able to enhance this activity in six out of nine normal donors considered. The possible therapeutical implications of these data are discussed.

Adjuvants, Immunologic↗

Role of thymic hormones in neuroimmunomodulation. Their use in patients with phobic disorders.

Many evidences support the existence of a bilateral connection between the thymic gland and the hypothalamic-pituitary-adrenal axis (HPAA). In this respect, neurohormones such as the adrenal corticotropin hormone and glucocorticoids cause thymic involution, while the growth hormone and the prolactin upregulate thymic functions. On the other hand, a thymic hormone, the thymosin fraction 5, activates the HPAA, thus closing-up the regulatory loop between immune system and nervous system. In this review, a clinical trial with two thymic hormones (Timostimolina and Thymopentin) in agoraphobic patients with phagocytic dysfunctions is reported. Results obtained indicate that both substances lead to a partial and temporary immunological recovery, since a further depression of phagocytic activities occurs in coincidence with panic attack. The use of alternative immunomodulators in these patients is discussed.

Adjuvants, Immunologic↗

Evaluation of phagocyte functions, inflammatory lymphokine activities and in vitro antibody synthesis in patients with active and chronic pulmonary tuberculosis.

In fourteen patients with pulmonary tuberculosis (TBC) (seven active and seven chronic cases) non-specific immunity and B cell function were evaluated. Polymorphonuclear cell (PMN) and monocyte chemotaxis, phagocytosis and killing were depressed to a different extent regardless of the disease status. Additionally, determination of lymphocyte-derived chemotactic factor and leukocyte inhibitory factor activities indicated a reduced production of these two lymphokines. This may also explain the impairment of phagocyte functions. Furthermore, the frequency of T cell subsets was slightly modified except for the increased number of CD25+ cells. The in vitro antibody response was analysed in a plaque-forming cell system using pokeweed mitogen (PWM) as a polyclonal activator and purified protein derivative (PPD) as a specific antigen. Results show that in patients with active TBC the anti-PPD antibody response was markedly enhanced, while in both groups of patients PWM-induced antibody synthesis was normal. These findings indicate several immune deficiencies related to phase activity which occur during the course of the disease.

Adult↗

HIV-infection and in vivo lipopolysaccharide-induced release of cytokines. An amplified mechanism of damage to the host.

Bacterial lipopolysaccharides (LPS) or endotoxins are potent triggers of the cytokine (CK) cascade. These CKs are immune mediators which produce many biological effects and could play a detrimental rather than beneficial role in the host. In this review emphasis will be placed on the participation of two CKs, tumor necrosis factor [TNF-alpha and interleukin (IL-1) beta], in the pathogenetic development of HIV infection. We have found that TNF and IL-1 circulate in exaggerated amounts in the blood of HIV-infected subjects from the earliest phases of infection. Furthermore, we have observed a strict correlation between plasma LPS and IL-1 beta levels, thus indicating that endotoxins could account for the production of CKs in the course of HIV infection. Finally, the demyelinating role of TNF-alpha either in experimental models or in the course of AIDS dementia complex is outlined.

Animals↗

Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura?

Migraine without aura (MWA) is a clinical condition characterized by multiple immune deficits, which may play an important role in the pathogenesis of the disease. In this respect, previous studies have demonstrated that patients with MWA exhibit profound dysfunctions of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes. This may correlate with the increased frequency of infectious processes observed in these patients. The overall results suggested to evaluate the presence of circulating cytokines (CKs) in subjects affected by MWA. In particular, the present data point out an exaggerated spontaneous release of tumor necrosis factor (TNF)-alpha in a group of MWA individuals, which correlates with detectable levels of bacterial lipopolysaccharides (LPS) in their plasma. In view of the different biological activities displayed by TNF-alpha in the host, such as effects on the nervous and vascular systems, hemodynamics modifications and demyelinating properties, the intervention of this CK in the pathogenesis of MWA will be discussed.

Humans↗

The gamma subunit of F1 and the PVP protein of F0 (F0I) are components of the gate of the mitochondrial F0F1 H(+)-ATP synthase.

The gamma subunit of the F1 moiety of the bovine mitochondrial H(+)-ATP synthase is shown to function as a component of the gate. Addition of purified gamma subunit to F0-liposomes inhibits transmembrane proton conduction. This inhibition can be removed by the bifunctional thiol reagent diamide. Immunoblot analysis shows that the diamide effect is likely due to disulphide bridging of the gamma subunit with the PVP protein of the F0 sector.

Animals↗

T lymphocytes possess receptors for brain myelin small protein.

In immunomediated demyelinating diseases, T cells are found in chronic lesions. To discover whether immunocompetent cells may interact with some myelin proteins, we purified myelin proteins in the lipid-bound native state and evaluated their binding to peripheral blood mononuclear cells (PMBC) isolated from healthy donors. To this end, myelin proteins were conjugated to biotin and added to PBMCs or purified CD4+ and CD8+ cells; then binding was detected using fluoresceinated avidin. In this article, we describe experiments carried out with a myelin protein recently discovered in the central nervous system. Our results show that this small, phosphatidylserine-binding protein can bind to human T cells.

Antigens, Differentiation, T-Lymphocyte↗

Alterations of nonspecific immunity in patients with common migraine.

In 23 patients with common migraine (CM), immune responsiveness and frequency of immunocompetent cells were investigated. In particular, phagocytosis and killing of Candida albicans by polymorphs (PMNs) and monocytes were analyzed. Also, the percentages of CD3+, CD4+, CD8+, natural killer, and CD15+ cells were evaluated by direct immunofluorescence using specific monoclonal antibodies. The results showed deficits of phagocytosis or killing exhibited by PMNs and monocytes. These immunological findings are discussed in terms of perturbation of immune status in CM patients during migraine attacks.

Adult↗

Senile dementia, Alzheimer type: a distinct entity in the immunosenescence?

Since previous data have provided conflicting results on immunoresponsiveness in senile dementia, Alzheimer type (SDAT), we evaluated the immune function in groups of SDAT patients and aged and young donors. In comparison to the younger subjects, SDAT and aged subjects did not exhibit significant differences in lymphocyte surface markers. Both groups of aged donors showed decreased B cell polyclonal responsiveness in a nonspecific T cell-driven B lymphocyte differentiation system. The use of an antigen-specific induction assay revealed an imbalance of T helper (Th) or T suppressor function in the elderly, while SDAT individuals were characterized by decreased Th activity. At the same time, aged individuals manifested an impairment of leukocyte-inhibiting factor (LIF) and lymphocyte-derived chemotactic factor production; a selective deficit of LIF release was seen in SDAT. Finally, elderly individuals displayed a decline of polymorphonuclear cell (PMN)-mediated functions and monocyte phagocytosis; only a decrease in PMN response was observed in SDAT. These results reveal discrepancies in impaired immune responses between SDAT and aging.

Adult↗

Report of the symposium on the use of intravenous gammaglobulin in adults infected with the human immunodeficiency virus.

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with IVIG, and Section 4 examines the major differences between IVIG and hyperimmunoglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of IVIG in association with low-dose or standard-dose zidovudine (AZT).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of bacterial lipopolysaccharides in the development of natural antibacterial activity mediated by human peripheral blood T lymphocytes.

The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhi activity. In nonendemic areas for salmonellosis this activity is exerted by CD4+ lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+ lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity. In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms of Salmonella LPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition. Finally, fractionation of PBL by means of S. minnesota R345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhi activity. The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells.

Adult↗

Administration of thymopentin to patients with phobic disorders improves depressed phagocytic functions.

Seven patients with phobic disorders were administered with a synthetic thymic extract, thymopentin (TP-5), in order to correct depressed polymorphonuclear cell (PMN) and monocyte phagocytosis and killing capacities. Subcutaneous administration (50 mg, three times weekly, for a period of 8 wks) of TP-5 resulted in a significant increase in phagocytic function with no change in the phagocytic capacity of PMN. These data support the concept that immunomodulators can achieve a correction of immune deficiencies associated with phobic disorders.

Adult↗

Studies on lymphokine production in lepromatous leprosy patients.

In order to evaluate whether lymphokine (LK) release is impaired in patients with lepromatous leprosy (LL), the production of two LKs, namely leukocyte inhibitory factor (LIF) and interleukin-2 (IL-2) from peripheral blood mononuclear cells of LL individuals was investigated. Results show that in eight patients CD4+ cells exhibit a reduced release of LIF, while CD8+ lymphocytes are still able to secrete this LK. In the remaining three patients both CD4+ and CD8+ cells produced LIF as do normal lymphocyte subpopulations. As far as IL-2 release is concerned, all patients fail to produce the above LK either using purified CD4+ or CD8+ lymphocytes. These data emphasize additional defects in immune responsiveness in leprosy.

Adult↗