The potential role of interleukin-37 in infectious diseases.

Interleukin-37 (IL-37) is a newly introduced cytokine to interleukin-1 family. Many studies have demonstrated that IL-37 owns immunosuppressive effects against both innate and acquired immune responses via inhibition of several inflammatory mediators. Thence, IL-37 has anti-inflammatory action in some diseases including cancer, autoimmune diseases, cardiovascular diseases and infectious diseases. Recent investigations have reported the important role of IL-37 in immunity against viral, bacterial and fungal infections as they prevent inappropriate immune activation and suppress the inflammation induced by these infectious agents. Thus, IL-37 could play a crucial role in protecting host tissues from injury during infections by damping excessive inflammatory reactions. However, the precise roles of IL-37 in infectious diseases remain largely unknown. The current review shed light on the pivotal role of IL-37 in infectious diseases such as the human immunodeficiency virus-1 (HIV-1), viral myocarditis, hepatitis C virus (HCV), hepatitis B virus (HBV), tuberculosis, leprosy, pneumococcal pneumonia, listeria infection, aspergillosis, candidiasis and eumycetoma. In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease.

Antiphospholipid antibodies, antiphospholipid syndrome and infections.

Since the association between antiphospholipid antibodies (aPL) and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies (aCL). A review of the literature shows that while aCL occur frequently in viral infections, particularly in HIV (49.75%), HBV (24%) and HCV (20%), it is very rarely associated with anti-beta2 glycoprotein I antibodies (anti-beta2GPI) and is not correlated with thrombosis risk or hematological manifestations of the antiphospholipid syndrome (APS). Concerning bacterial infections, aCL is often present in leprosy (42.7%), where it is frequently associated with the presence of anti-beta2GPI (44.8%), and in syphilis infections (8 to 67%), though without correlation with thrombotic events. Though few individual patients with unequivocal infection-induced aPL satisfy criteria for APS, the lack of statistical association with thrombotic events strongly argues against the identification of a true APS subset in this context. However, physicians should keep in mind the fact that an infection, generally bacterial, in patients with confirmed APS, may lead to catastrophic antiphospholipid syndrome with a possible fatal outcome.

Use of live Saccharomyces cerevisiae cells as a biological response modifier in experimental infections.

A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae. S. pneumoniae and S. pyogenes A produced by intranasal inoculation. Yeast pre-treatment also increased the efficacy of antibiotic therapy in bacterial infections and of antiviral drugs in viral infections. Yeast treatment of animals stimulated phagocytosis, activated the complement system and induced interferon which are likely to represent the main mechanisms of action whereby pretreatment of mice with live S. cerevisiae cells increases resistance to infection. It is concluded that preventive administration of live Saccharomyces cerevisiae cells should be used for increasing resistance to bacterial infections, in particular of the respiratory tract, or to viral infections, as well as an adjunct to antibiotic and antiviral drug therapy.

[Analysis of T-cell subpopulations. Pathophysiological concept and significance for clinical medicine]. / Analyse von T-Zell-Subpopulationen. Pathophysiologisches Konzept und Bedeutung für die Klinik.

Two T-lymphocyte subsets develop in the thymus which differ in the expression of glycoproteins on their cell surface. About 60% of the circulating T cells express the glycoprotein T4, while about 30% have the glycoprotein T8. T4 and T8 cells can be determined in the peripheral blood or various organs with monoclonal antibodies. T4 and T8 cells differ in their antigen recognition, have different functions, and can cause various pathohistological changes. T4 cells recognize the antigen in association with the HLA-D/DR/DP determinants. Upon antigenic stimulation they liberate various factors and initiate and amplify an immune response (T4 = helper/inducer T-cells). They can also be cytotoxic and are mediating effector functions via macrophage activation. T8 cells recognize the antigen in association with HLA-A/B/C determinants. They exert their cytotoxic or suppressive effector functions mainly in viral infections. The T4 or T8 cell-mediated pathohistological changes are discussed in the light of the well studied T-cell infiltrations in lepra lepromatosa or lepra tuberculosa. The T4/T8 cell dyscrasia in the peripheral blood, described in a variety of infectious, autoimmune or immunodeficiency diseases, may be due to enhanced proliferation, selective sequestration, reduced production or the elimination of a subset. T-cell subset analysis in joints, bronchial lavages and tissues has clarified the pathomechanism in a variety of autoimmune diseases, although the etiology remains obscure. For example, in rheumatoid arthritis, multiple sclerosis, and sarcoidosis, a T4 cell-mediated reaction with macrophage activation can be found. T4/T8 cell analysis may also be of value in dissecting heterogenous diseases, e.g. systemic lupus erythematosus. Of value is also the additional demonstration of membrane components reflecting T-cell activation (IL-2 receptor or DR-antigen expression) which serves to identify the activated T-cell subset in peripheral blood. Finally, T4/T8 cell analysis can be helpful in deciding treatment, as the T-cell subsets have a different sensitivity to immunosuppressive drugs.

Symposium on the immunodiagnosis of rheumatic and related diseases, Part II. Rheumatoid factors.

Human rheumatoid factors are antibodies of IgG, IgA, or IgM class that show reactions with antigenic determinants present on other immunoglobulin molecules. The most commonly measured rheumatoid factor relates to the 19S IgM type, which reacts by agglutination of latex particles coated with 7S IgG and is often measured in the standard latex fixation test. Approximately 65 to 70 per cent of patients with rheumatoid arthritis show positive serologic tests for rheumatoid factor; however, a number of other chronic disease conditions are also associated with positive rheumatoid factor reactions, including infective endocarditis, sarcoidosis, leprosy, and other hyperglobulinemic conditions. Although extensive serologic and immunochemical studies have identified a number of specific antigenic structural sites on immunoglobulin molecules that react with rheumatoid factors, recent studies have shown that a certain proportion of such antibodies may show cross-reactivity with DNA-histone complexes as well. It is still not entirely clear how rheumatoid factors fit into the pathogenesis of rheumatoid arthritis itself.

Soluble immune complexes in human disease.

The great variety in biochemical properties of immune complexes occurring in human and animal disease states has made the detection of such complexes a difficult task. Variability in immune complex size, specificity, and interaction with humoral or cellular receptor systems, such as complement and phagocytes, suggests different pathogenic properties. The introduction of radioimmunoassays and the recently improved knowledge of the immune complex-receptor interactions have lead to the description of a large number of detection procedures, which in turn has widened the catalogue of diseases associated with immune complexes. This widespread occurrence of soluble immune complexes has lead many investigators to think that such complexes may occur either as a transient physiological phenomenon, important for fast clearance of the antigen, or as primary pathogenic factors triggering inflammatory reactions. Among the 50 procedures for immune complex detection known today, the article will select some pertinent tests, which will be discussed with respect to their specificity, sensitivity, and reproducibility. Furthermore, it is well known that when applied to the study of a patient group with one particular immune complex disease, various tests will result in different percentages of patients having complexes. This observation is due to differences in the underlying principle on which the various tests are based. Thus immune complexes must be further characterized with respect to their size, to the antibody class or specificity involved and, most difficult, to the antigenic specificity which participates in the complex. Recent advances in such experimental characterization of immune complexes in vitro and in the clinical evaluation of patients with complement activation associated to the presence of immune complexes will be discussed.