Action of mannitol in various immunological experimental models

The authors describe the inhibiting action of mannitol after repeated administration of low subcutaneous doses in a number of experimental immunological models. For example, in the rat it produces a reduction of the secondary arthritis of Freund's adjuvant polyarthritis and also of the pleurisy due toBordetella pertussis hypersensitivity. In the mouse it reduces the reaction of delayed hypersensitivity to sheep red cells. Its action is also marked against ovalbumin-induced active skin anaphylaxis in the albino guinea-pig and on IgE synthesis in the rat.Moreover, after several injections it produces a reduction of carbon phagocytosis in the mouse.At the doses at which the effect appeared, no action could be found on various models of acute non-immune inflammation, diuresis, blood pressure, hematocrit and protein and plasma sodium levels     

The immunological basis of inflammatory diseases

Most immunologically-mediated diseases are inflammatory in nature, as assessed by cellular infiltrates at the lesion site. Recent immunohistological studies using monoclonal antibodies on tissue sections and synovial or cerebrospinal fluid reveal that B- and T-lymphocytes (predominantly T) participate in this reaction, together with monocytes and macrophages. The etiopathogenesis of inflammatory diseases of immunological origin can be discussed at two levels. (1)Lesions may be secondary to the cytopathic effect of antibodies, either by direct cytolysis or by opsonization, antigenic modulation, or blockage of functionally-relevant molecules. Immune complexes formed in the circulation or locally at the lesion site may intervene. Direct cellular mechanisms are probably involved, as suggested by evidence in hepatitis (indirect) and in juvenile insulin-dependent diabetes (direct). K-cells may act by antibody-dependent cytotoxic'ty, paritularly in autoimmune diabetes and thyroiditis where lymphocyte-dependent antibodies are demonstrated. Unfortunately, the absence of adequate markers does not permit adequate detection of K-cells in inflammatory reaction sites. (2)Etiological factors are multiple in a given disease and even in a single patient. Deficiency of suppressor T-cells, assessed using monoclonal anti T-cell antibodies, represents a major predisposing factor, although suppressor cell deficit may be restricted to some antigens (EBV) in certain patients. The deficiency of interleukin-2 production in lupus and rheumatoid arthritis is intriguing but the mechanism and its relationship to disease etiology are unknown. Other immunological factors include intrinsic B-cell hyperactivity, anti-T-cell auto-antibodies, and complement deficiencies, whereas non-immunological factors such as viruses, drugs or sex hormones are important but ill-defined. The treatment of immunologically-mediated inflammatory diseases can be considered at several levels. Anti-inflammatory agents act peripherally, and where only anti-inflammatory action is needed, NSAIDs should be used. Immunosuppressive agents act non-specifically and a better appreciation of their respective immunosuppressive and anti-inflammatory actions is required, especially for steroids. More selective drugs are needed, such as cyclosporin A which acts selectively on helper T-ce!ls or monoclonal anti-T-cell antibodies. Immunomodulating drugs such as the thymic hormones, which would allow restoration of the physiological T-cell balance, represent a new approach and preliminary data in murine lupus and human rheumatoid arthritis are promising.     

Action of morphine on reproduction and immunological status in mice

The course of embryogenesis is disturbed in CBA mice during prolonged administration of morphine. There is a parallel decrease in the level of antibody-synthesizing cells and a significant fall in cooperative interaction between T-and B-lymphocytes in response to injection of sheep's red blood cells. Meanwhile stimulation of bone marrow cells and specific sensitization of producers of migration inhibition factor to antigen from the brain of mice treated with morphine are observed.Research Laboratory of Experimental Immunobiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 465–467, October, 1979.     

Photostability of some carbenium salts

The photolysis of triphenylmethyl salts with anions such as SbCl, FeCl and AsF was investigated in inert and oxygen atmosphere. On irradiation by visible light the characteristic bands of the cation disappeared in 20 min and in 15 h at concentrations of 10^?4 M and 10^?3 M , respectively. The main photolytes identified were triphenylmethane, triphenylchloromethane, triphenylcarbinol, benzophenone, fluorenone, fluorene, 9-hydroxy-9-phenylfluorene, 9-phenylfluorene besides 2–3% nonidentified products. The results showed that the product composition of the photolyzed mixture depended only slightly on the atmosphere used, the differences in the amounts of the products being more significant.     

Current status of redox markers in immunological and inflammatory diseases

Overloads of reactive oxygen species (ROS), including superoxide, hydrogen peroxide and hydroxyl radical, that exceed the capacity of antioxidant systems induce oxidative stress in the body. Accumulating evidence suggests that ROS play a critical role in the pathogenesis of immunological and inflammatory diseases. Excessive exposure to ROS is the hallmark of oxidative stress and leads to damage of lipids, proteins and nucleic acids. Recently, specific redox (i.e., reduction/oxidation) biomarkers for oxidative damage and antioxidant defenses have been introduced into the field of clinical and laboratory medicine. This brief review discusses the rapidly accruing data linking oxidative events as critical participants in immunological and inflammatory diseases, including atopic dermatitis, bronchial asthma, systemic inflammatory response syndrome and diabetes mellitus. Data from our recent clinical and experimental studies are presented. Studies evaluating the efficacy of antioxidant substances in the prevention and treatment of the diseases are reviewed, and suggestions are made for the direction of future studies.     

Comparative ultrastructural morphology of aurosomes produced by colloidal gold and soluble gold salts.

Intra-articular administration of colloidal gold produced aurosomes which contained spherical electron-dense granules and also often some very fine electron-dense particles. Intra-articular administration of aurothioglucose produced aurosomes of a morphology similar to that reported to occur after administration of sodium aurothiomalate. These aurosomes produced by soluble gold salts are characterised by particle and granule-studded membranous formations which present in profile as rod-like and curled filamentous structures. On the basis of morphological differences two types of aurosomes should be recognised, the "Type I or granular aurosome" and the "Type II or membranous aurosome".     

The value of theoretical models in immunological research

With the increase in understanding of immunological phenomena has come an increase in availability of mathematical models which describe them. Here Judith Rae Lumb argues that theoretical models should be more widely appreciated and used, especially since helpful computer programs are now becoming available.     

Studies on the anti-inflammatory and immunotropic effect of gold salts

The experiments carried out in vitro and in vivo aimed at evaluation of the effect of the selected gold salts on the experimental inflammatory reactions and cellular immune reactions, specific and nonspecific. The preparations investigated appeared to inhibit relatively weakly nonspecific inflammatory processes (granulation test, lysozym level) but to strongly inhibit the cellular immune reactions (GvH reaction, LNPF test, contact hypersensitivity). The possible mechanisms of the gold salts effect are discussed which were shown neither to consist in the stabilization of cell membranes nor to act through the thymus factors or the influence on quantitative relations between T and B lymphocytes. A suggestion has been put forward that gold salts exert direct effect on the mature final cells participating in the immune processes.     

Intracellular accumulation and immunological properties of fluorescent gold nanoclusters in human dendritic cells

We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (∅ < 3 nm) stabilized by different ligands on the intracellular accumulation and immune response of human derived-monocyte dendritic cells (DCs). Results indicate that the high uptake efficiency of Au NCs is strongly related to their small size and to the nature of the ligand, with zwitterionic ligands being more effective than PEGylated ones. Evidence from flow cytometry and microscopy demonstrate time and concentration-dependent Au NCs internalization by endocytic pathway(s) involving amorphous and laminar organelles, while maintaining their discrete size and photoluminescence properties. The uptake of zwitterionic ligand-stabilized Au NCs induced very low cytotoxicity and a strong immunosuppressive response (Th1/Treg pattern), associated with a DC maturation state. This behavior contrasts to the effect of bigger particles (∼12 nm size) which induced a cytotoxic response involving Natural Killer (CD56) cells. Overall, this study stresses the critical importance of particle size and ligand type on the immunostimulation of DCs and highlights the remarkable potential of this new class of nanomaterial as a novel vaccine platform.     

Animal models of allergic and inflammatory conjunctivitis

Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small number of allergens such as ovalbumin, ragweed pollen or major cat allergens and consecutive challenge. Different animal species have been used so far. Starting with guinea-pig models of allergic conjunctivitis to assess pharmacological aspects, new models including rats and mice have been developed which mimic major features of ocular allergy. The presently preferred species for the investigation of the immunological basis of the disease is represented by murine models of allergic conjunctivitis. In the future, combined ocular, nasal and aerosolic challenges with allergens may provide a model of allergy that encompasses simultaneously the target organs eye, nose and airways with conjunctivitis, rhinitis and asthma.     

Animal models and possible human application of immunological restoration in the elderly

Autopsy reports by pathologists in geriatric hospitals reveal that the leading direct cause of death in the elderly over 65 years of age are infectious diseases such as pneumonia and urinary tract infection, neither cancer nor vascular diseases in the brain and heart. This indicates that severe impairment of immune functions is developing in the elderly people. The impairment of immune functions does not occur abruptly in the elderly people. The immune function starts to decline as early as at the 2nd decades, showing approximately 50 and 90% decline at the 5th and 8th decades, respectively. Thus, immunological restoration is acutely needed for the improvement of their general health condition of the elderly. This report communicates several methods of immunological restoration using animal models and suggests possibilities of human application. Methods presented are: (1) a low dose of cyclophosphamide; (2) vitamin E; (3) Japanese herbal medicines; (4) caloric restriction and exercise; (5) vaccine; (6) oral administration of antigens; (7) grafting of cells and tissues, including a future program. Discussion will be made on the possibilities of these methods for human application.     

Experimental models of inflammatory bowel disease

The etiology and pathogenesis of inflammatory bowel disease (IBD) remains unsolved, but improved experimental models of enterocolitis have led to progress. Intestinal inflammation and experimental IBD can be induced by chemical or dietary factors or by microbial products. Many animal models of IBD can be used to evaluate new anti-inflammatory drugs. These models, however, usually demonstrate acute, self-limiting colitis. The spontaneous colitis models developed in the cotton-top tamarin monkey and the C3H/HeJBir mouse mimic more features of human IBD. Inflammation is chronic and is under genetic control. The differential genetic susceptibility of inbred rat strains to chronic inflammation have been exploited. Lewis rats injected with bacterial products, peptidoglycan polysaccharide or indomethicin develop chronic relapsing enterocolitis, whereas closely related Buffalo or Fisher rat strains develop only transient inflammation. These models are also useful to test the specific inhibition of inflammatory mediators and target molecules. Over-expression (transgenic) or deletion (knockout) of specific genes have led to the development of rodent models of spontaneous colitis. Inflammation arises from a number of mutations of immunomodulatory molecules, supporting the concept of genetic heterogeneity for IBD. The results obtained from experimental models have generated new hypotheses, expanded human studies, and suggested novel forms of therapy for IBD patients.