Holger Kirchner

Bio: Holger Kirchner is an academic researcher from University of Lübeck. The author has contributed to research in topics: Interferon & Virus. The author has an hindex of 60, co-authored 322 publications receiving 12623 citations. Previous affiliations of Holger Kirchner include German Cancer Research Center.

Antiviral effects of recombinant tumour necrosis factor in vitro

Abstract: Tumour necrosis factor (TNF) was first described as a factor in the serum of mice injected with tubercle bacilli (BCG) and several days later with lipopolysaccharide (LPS). The gene encoding TNF has recently been cloned and pure recombinant human TNF is now available. TNF is known for its in vivo antitumour effect and in vitro cytotoxicity on certain transformed cell lines. Similarities in amino acid sequence and biological activity to lymphotoxin and cachectin have been reported, and very recently a growth-factor-like activity on diploid fibroblasts was observed. There is no similarity between these proteins and interferons (IFNs), which are also induced during in vivo induction of TNF. Here we describe the antiviral activity of pure recombinant human TNF in a typical in vitro antiviral assay which we discovered while investigating the possible role of TNF as an inducer of IFN.

Association between clinical disease activity and Epstein–Barr virus reactivation in MS

Abstract: Objective: To assess the potential significance of Epstein–Barr virus (EBV) reactivation in disease activity in MS patients. Methods: The prevalence of antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy control subjects. Sera were analyzed using combinations of novel assay systems employing highly purified viral and recombinant antigens. In addition, PCR for the detection of EBV DNA was performed in serial samples. Results: In contrast to the control populations, antibodies against EBV were present in 100% of MS patients. Among the tested human herpesviruses, this high extent of seropositivity was only found for EBV. Primary infection was found exclusively in the control group (3.7%), whereas serologic evidence of EBV reactivation was seen in MS patients (13.9%) as well as control subjects (17.2%). There was no temporal coincidence between EBV reactivation and disease activity in MS patients. However, in 19 patients followed monthly for 1 year, active viral replication as measured by increased immunoglobulin (Ig) M and IgA responses to EBV early antigens (p54 + p138) and positive serum DNA was seen in 72.7% of patients with exacerbations during the study period and in none of the patients with clinically stable disease. Conclusions: The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

Cytokine production and serum proteins in depression.

Abstract: One, as yet unemployed, approach to investigating immunology in depression is the assessment of the cytokine production by leucocytes, which would allow the determination of immune response under standardized conditions. Thus we measured the production of mitogen-induced cytokines (IL-1 beta, IL-2, IL-6, IL-10, interferon-gamma) and sIL-2R in a whole blood assay, and serum protein levels such as C-reactive protein (CRP), haptoglobin (Hp) and alpha 2-macroglobulin (alpha 2 M) in a longitudinal 6-week study in an attempt to assess leucocyte function during and after acute clinical stage of depression in 39 patients. Shortly after admission to hospital we found higher levels of all measured cytokines in the patients. Serum protein levels were significantly higher in the patients than in controls, and decreased over the study period. Whereas slightly elevated monokine levels in patients tended to reach control values, lymphokines showed a significant decrease over the 6 weeks as compared to baseline. These results suggest that the increase in immune activity seen at the beginning of the study may be followed by a suppressed cell-mediated immune function.

Zinc-Altered Immune Function and Cytokine Production

Abstract: Although the intriguing role of zinc as an essential trace element for immune function is well established, particular progress in determining the molecular principles of action of this ion was made recently. Leukocyte responsiveness is delicately regulated by zinc concentration. Zinc deficiency as well as supraphysiologic levels impair immune function. Furthermore, the activities of many immunostimulants frequently used in immunologic studies are influenced by zinc concentration. Therefore, our knowledge from in vitro studies is widely dependent on the zinc concentration, and when not in physiologic range, immunologic responses are artificially low. Decreased production of TH1 cytokines and interferon-alpha by leukocytes in the healthy elderly person is correlated with low zinc serum level. The defect in interferon-alpha production is reconstituted by the addition of physiologic amounts of zinc in vitro. Interestingly, zinc induces cytokine production by isolated leukocytes. Zinc induces monocytes to produce interleukin-1, interleukin-6 and tumor necrosis factor-alpha in peripheral blood mononuclear cells and separated monocytes. This effect is higher in serum-free medium. However, only in the presence of serum does zinc also induce T cells to produce lymphokines. This effect on T cells is mediated by cytokines produced by monocytes. Stimulation also requires cell-to-cell contact of monocytes and T cells. Information is presented to illustrate the concepts that the zinc concentration must be taken into account whenever in vitro studies are made or complex alterations of immune functions are observed in vivo.

Biology of natural killer cells.

Abstract: Publisher Summary Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.

Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts.

Abstract: Background Medication toxic effects and drug-related problems can have profound medical and safety consequences for older adults and economically affect the health care system. The purpose of this initiative was to revise and update the Beers criteria for potentially inappropriate medication use in adults 65 years and older in the United States. Methods This study used a modified Delphi method, a set of procedures and methods for formulating a group judgment for a subject matter in which precise information is lacking. The criteria reviewed covered 2 types of statements: (1) medications or medication classes thatshould generally be avoidedin persons 65 years or older because they are either ineffective or they pose unnecessarily high risk for older persons and a safer alternative is available and (2) medications that should not be used in older persons known to havespecific medical conditions. Results This study identified 48 individual medications or classes of medications to avoid in older adults and their potential concerns and 20 diseases/conditions and medications to be avoided in older adults with these conditions. Of these potentially inappropriate drugs, 66 were considered by the panel to have adverse outcomes of high severity. Conclusions This study is an important update of previously established criteria that have been widely used and cited. The application of the Beers criteria and other tools for identifying potentially inappropriate medication use will continue to enable providers to plan interventions for decreasing both drug-related costs and overall costs and thus minimize drug-related problems.