caa a22 4500 397591586 CHVBK 20180308164940.0 cr unu---uuuuu 161202e199608 xx s 000 0 eng 10.1093/jac/38.2.167 doi (NATIONALLICENCE)oxford-10.1093/jac/38.2.167 Issues in the adjunct therapy of severe sepsis [Elektronische Daten] [Jan Verhoef, Willem M. N. Hustinx, Helma Frasa, Andy I. M. Hoepelman] Until recently the concept of immunomodulation in patients with severe sepsis (formerly called sepsis syndrome or septic shock) appeared very promising. Research has focused on the possible therapeutic potential of interfering with cytokine pathways, either by preventing the induction of cytokines, such as TNF-a, by neutralization of lipopolysaccharide (LPS), or through the use of agents that attenuate cytokine action. Nowadays research on protein or protein constructs with antibacterial activities such as bacterial/permeability increasing protein (BPI), platelet activating factor receptor antagonists, nitric oxide and cyclo-oxygenase inhibitors, are still being followed. In large clinical trials monoclonal antibodies against core glycolipid (E5, HAIA) were shown to be at best of only marginal benefit, and in some trials results were indecisive. Also, the results with IL-lra, although initially heralded with high expectation, were at the end disappointing and the trials discontinued. Two large trials with monoclonal antibodies against TNF showed some effect in subcategories of patients; a third trial is on its way. Other phase I, II studies include those of soluble TNF receptors and BPI. The area of immunomodulation has now become an area of more realism and the results of early trials has forced investigators to go back to the drawing board and to re-investigate the whole concept of immunotherapy and immunoprophylaxis. © 1996 by the British Society for Antimicrobial Chemotherapy Review nationallicence Verhoef Jan Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut Hustinx Willem M. N. Department of Medicine, Division Infectious Diseases, University Hospital Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut Frasa Helma Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut Hoepelman Andy I. M. Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut Journal of Antimicrobial Chemotherapy Oxford University Press 38/2(1996-08), 167-182 0305-7453 38:2<167 1996 38 jac https://doi.org/10.1093/jac/38.2.167 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/38.2.167 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Verhoef Jan Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Hustinx Willem M. N. Department of Medicine, Division Infectious Diseases, University Hospital Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Frasa Helma Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Hoepelman Andy I. M. Eijkman-Winkler Institute of Medical & Clinical Microbiology Heidelberglaan 100, 3584 CD Utrecht, The Netherlands aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 38/2(1996-08), 167-182 0305-7453 38:2<167 1996 38 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford