[Update on the epidemiology, diagnosis and therapy of tuberculosis in HIV-infected patients]. / Aktuelle Aspekte zur Epidemiologie, Diagnose und Therapie der Tuberkulose bei HIV-infizierten Patienten.

Globally, the diagnosis and treatment of tuberculosis (TB) in HIV-co-infection has improved dramatically over the last 10 years. Nonetheless, the mortality of co-infected patients remains elevated. In European countries, the proportion of HIV-infected patients amongst all TB cases varies greatly; in Germany it is about 4 - 5%. HIV-infection changes the molecular epidemiology of TB and the drug resistance situation. In endemic areas, HIV-infected patients are often re-infected after completion of treatment for active TB. HIV has a profound influence on the anti-TB-immune response and antiretroviral therapy (ART) cannot completely restore normal immune function. The clinical presentation in advanced HIV-infection is atypical and disseminated disease is common. New "Point-of-Care" test methods are poised to improve the diagnoses of TB in HIV-infection; however, further research is required. The treatment of co-infection is complicated by drug interactions and the immune reconstitution syndrome (IRIS). New concepts and treatment regimens for chemoprevention of TB are necessary, especially for HIV-infected persons.

Immune therapy for infectious diseases at the dawn of the 21st century: the past, present and future role of antibody therapy, therapeutic vaccination and biological response modifiers.

In the last decades of the 20th century, infectious diseases have re-emerged as a significant public health problem in the developed world. However, the available anti-infective armamentarium has proven to be alarmingly insufficient to combat many of the microbes that cause these diseases, such as drug resistant microbes, microbes for which therapy is not available or ineffective because of underlying host immune impairment, and microbes that only cause disease in the setting of impaired immunity but are not pathogens in normal individuals. Hence, there is an urgent need for new approaches to the treatment of infectious diseases that can increase the efficacy of anti-infective therapy and bolster the immune response to microbial agents in immunocompromised hosts, circumvent rising rates of antimicrobial drug resistance and be rapidly developed to fight emerging epidemics. Immune therapy, which encompasses pathogen-specific and non-pathogen specific modalities designed to augment or restore host immunity against disease causing microbes, are poised to play an important part in modern anti-infective therapy. Our growing understanding of host-microbe interaction and mechanisms of protective immunity have allowed for an increasingly rational approach to the design of immune based therapeutic modalities. As part of this effort, it is important to remember that the origin of modern anti-infective therapy was serum therapy, a pathogen-specific immune therapeutic modality. In this paper, we review the historical underpinnings and present and future applications of immune therapy for infectious diseases in light of current challenges to the field.

Interleukin-10: effects on phagocytosis and adhesion molecule expression of granulocytes and monocytes in a comparison with prednisolone.

Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.