[Trauma research net of the German Society for Orthopaedics and Trauma Surgery]. / Netzwerk Traumaforschung der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie.

A first meeting of the recently founded "Trauma Research Net" of the German Society for Orthopaedics and Trauma Surgery (DGOU e.V.) took place at the Reisensburg Castle, Günzburg, from 24 to 26 February 2011. Numerous representatives of trauma-related Research Institutes and University Hospitals in Germany demonstrated their main research foci. There was also an open discussion of current problems in trauma research, especially the lack of junior researchers and nationwide collaborations as well as limited information about the research topics of individual research groups. The overall research efforts of the "Trauma Research Net" apparently focus on fracture, multiple injury and inflammation on an organ and cellular level. Furthermore, an up-to-date matrix of the existing methods has been generated which is now provided for the networker. The common middle-term goal of the "Trauma Research Net" is the inclusive, intensive scientific exchange as well as the generation and workup of common hypotheses using standard operating procedures. In the long term, the resulting clustered research activities are intended to address and resolve clinically relevant questions in the field of trauma research.

Immune response of severely injured patients--influence of surgical intervention and therapeutic impact.

BACKGROUND: [corrected] Severe injury leads to a severe deterioration of the patients' immune response. The changes of the immune response after severe injury include a broad range of immune functions and may result in a status of immunosuppression, which could favor infectious complications. Therefore, immunostimulating therapies have been introduced in the therapy for severely injured patients in clinical and experimental settings. OBJECTIVES: The article summarizes actual immunomodulating approaches in the treatment of trauma patients and therapeutic strategies avoiding additional immune deteriorations. RESULTS: Examples for an immunostimulating approach in trauma patients are interferon gamma and the granulocyte macrophage-colony-stimulating factor (GM-CSF), which are summarized in this review in detail. However, the effect of such an interference in the patients' immune response with all its different cellular targets is not yet clearly understood, and most studies focus on the reaction of circulating monocytes. In addition, further immunomodulating strategies, including nutritional support, are addressed. However, clinically established therapeutic immunomodulating strategies in trauma care so far do not exist. The impact of the accidental and also an additional surgical trauma on the immune response has been clearly demonstrated. Therefore, the idea of a "damage control orthopedic surgery" (DCOS) is not only necessary to prevent further deterioration of the homeostasis of, e.g., the coagulating system, but is also desirable in terms of minimizing the burden on the immune system. In addition, also the timing of secondary surgical treatment in trauma patient care should include an evaluation of the immune response, although the most reliable markers still need to be identified. CONCLUSION: Immunomodulating therapies in trauma patients exist on an experimental level with inconsistent results. The general management of trauma patients includes strategies that have been developed also on the basis of immunological considerations.

A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice.

Dietary antigens are candidate environmental factors in the pathogenesis of type 1 diabetes. In the non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, cereal-based diets promote disease development, whereas the diets based on hydrolysed proteins or non-diabetogenic proteins are protective. The hypothesis that diabetogenic diets modulate the cytokine balance in the gut was tested. NOD mice were fed with NTP-2000 (mainly a wheat-based milk-free diet) or Prosobee (a semi-purified hypoallergenic diet based on soy protein isolate) or Prosobee plus casein (milk protein fraction). The mRNA levels of IFN-gamma, IL-10, TNF-alpha, TGF-beta, and inducible NO synthase in the small intestine and the Peyer's patches were determined by semi-quantitative RT-PCR. Mice fed on the cereal-based NTP-2000 diet expressed higher levels of the Th1-type and pro-inflammatory markers IFN-gamma, TNF-alpha, and inducible NO synthase mRNA compared to the Prosobee-fed animals. The expression of the counterregulatory cytokines IL-10 and TGF-beta was unaffected. This resulted in a significant bias of the intestinal cytokine balance towards T helper cell type 1 after feeding NTP-2000. The cytokine mRNA levels in the gut-associated Peyer's patches were not affected. Thus, modulation of gut immunoreactivity by diet may contribute to disease development in NOD mice.

Orally administered lead chloride induces bias of mucosal immunity.

The hypothesis that lead disturbs gut immune functions upon oral ingestion was tested. Long-term exposure to oral PbCl(2)for 10 days caused persistent downregulation of TGF-beta mRNA levels in intestinal tissue. PbCl(2) also disturbed oral tolerance induction to the dietary antigen ovalbumin. Upon challenge with an immunizing dose of ovalbumin and rechallenge of draining lymph node cells in vitro, tolerance induction was partially suppressed in animals exposed to oral PbCl(2). This was shown by increased proliferation to antigenic stimulus, increased production of IFN-gamma and decreased secretion of TGF-beta. In conclusion, we show for the first time that oral exposure to PbCl(2)has a significant effect on the gut immune system, demonstrated by a bias of the cytokine pattern towards Th(1)and by disturbed oral tolerance mechanisms.

Antigen-pulsed epidermal Langerhans cells protect susceptible mice from infection with the intracellular parasite Leishmania major.

Efficient vaccination against the parasite Leishmania major, the causative agent of human cutaneous leishmaniasis, requires the development of a resistance-promoting CD4+-mediated Th1 response. Epidermal Langerhans cells (LC) are critically involved in the induction of the primary immune response to Leishmania infection. They are able to ingest the parasites, to express MHC class II molecules with extraordinarily long half-life and to activate naive L. major-specific Th cells. Considering these unique properties, we studied the capacity of LC to mediate resistance to L. major in vivo. A single i.v. application of LC that had been pulsed with L. major antigen in vitro induced the protection in susceptible BALB/c mice against subsequent challenges with L. major parasites. Resistance could neither be induced by unpulsed LC, nor by L. major antigen alone or by L. major-pulsed macrophages. Development of resistance was paralleled by a reduced parasite burden and by a shift of the cytokine expression towards a Th1-like pattern. In contrast, control mice developed a Th2 response. In vitro exposure of LC to L. major antigen induced the expression of IL-12 (p40) mRNA. In conclusion, our data demonstrate that LC are able to serve as a natural adjuvant and to induce a protective immune response to L. major infection. This effect is based on the initiation of a Th1-like response that is likely to be mediated by IL-12.