Rosanna Vaschetto1, Nausicaa Clemente2, Aline Pagni3, Teresa Esposito4, Federico Longhini3, Francesca Mercalli5, Elena Boggio2, Renzo Boldorini5, Annalisa Chiocchetti2, Umberto Dianzani6, Paolo Navalesi7. 1. SCDU Anestesia e Rianimazione, Azienda Ospedaliero Universitaria "Maggiore della Carità", Novara, Italy. 2. IRCAD and Università del Piemonte Orientale "Amedeo Avogadro", Dipartimento di Scienze della Salute, Novara, Italy. 3. SC Anestesia e Rianimazione, Ospedale Sant'Andrea (ASL VC), Vercelli, Italy. 4. Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy. 5. SCDU Anatomia Patologica, Azienda Ospedaliero Universitaria "Maggiore della Carità", Novara, Italy. 6. IRCAD and Università del Piemonte Orientale "Amedeo Avogadro", Dipartimento di Scienze della Salute, Novara, Italy. Electronic address: umberto.dianzani@med.uniupo.it. 7. SC Anestesia e Rianimazione, Ospedale Sant'Andrea (ASL VC), Vercelli, Italy; Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy; CRRF Mons. L. Novarese, Moncrivello, VC, Italy.
Abstract
BACKGROUND: Patients with severe pneumonia often develop septic shock. IgM-enriched immunoglobulins have been proposed as a potential adjuvant therapy for septic shock. While in vitro data are available on the possible mechanisms of action of IgM-enriched immunoglobulins, the results of the in vivo experimental studies are non-univocal and, overall, unconvincing. We designed this double blinded randomized controlled study to test whether IgM-enriched immunoglobulins administered as rescue treatment in a pneumonia model developing shock, could either limit lung damage and/or contain systemic inflammatory response. METHODS: Thirty-eight Sprague Dawley rats were ventilated with injurious ventilation for 30min to prime the lung. The rats were subsequently randomized to received intratracheal instillation of either lipopolysaccharide (LPS) (12mg/kg) or placebo followed by 3.5h of protective mechanical ventilation. IgM-enriched immunoglobulins at 25mg/h (0.5mL/h) or saline were intravenously administered in the last hour of mechanical ventilation. During the experiment, gas exchange and hemodynamic measurements were recorded. Thereafter, the animals were sacrificed, and blood and organs were stored for cytokines measurements. RESULTS: Despite similar lung and hemodynamic findings, the administration of IgM-enriched immunoglobulins compared to placebo significantly modulates the inflammatory response by increasing IL-10 levels in the bloodstream and by decreasing TNF-α in bronchoalveolar lavage (BAL) fluid. Furthermore, in vitro data suggest that IgM-enriched immunoglobulins induce monocytes production of IL-10 after LPS stimulation. CONCLUSIONS: In an in vivo model of pneumonia developing shock, IgM-enriched immunoglobulins administered as rescue treatment enhance the anti-inflammatory response by increasing blood levels of IL-10 and reducing TNF-α in BAL fluid.
BACKGROUND:Patients with severe pneumonia often develop septic shock. IgM-enriched immunoglobulins have been proposed as a potential adjuvant therapy for septic shock. While in vitro data are available on the possible mechanisms of action of IgM-enriched immunoglobulins, the results of the in vivo experimental studies are non-univocal and, overall, unconvincing. We designed this double blinded randomized controlled study to test whether IgM-enriched immunoglobulins administered as rescue treatment in a pneumonia model developing shock, could either limit lung damage and/or contain systemic inflammatory response. METHODS: Thirty-eight Sprague Dawley rats were ventilated with injurious ventilation for 30min to prime the lung. The rats were subsequently randomized to received intratracheal instillation of either lipopolysaccharide (LPS) (12mg/kg) or placebo followed by 3.5h of protective mechanical ventilation. IgM-enriched immunoglobulins at 25mg/h (0.5mL/h) or saline were intravenously administered in the last hour of mechanical ventilation. During the experiment, gas exchange and hemodynamic measurements were recorded. Thereafter, the animals were sacrificed, and blood and organs were stored for cytokines measurements. RESULTS: Despite similar lung and hemodynamic findings, the administration of IgM-enriched immunoglobulins compared to placebo significantly modulates the inflammatory response by increasing IL-10 levels in the bloodstream and by decreasing TNF-α in bronchoalveolar lavage (BAL) fluid. Furthermore, in vitro data suggest that IgM-enriched immunoglobulins induce monocytes production of IL-10 after LPS stimulation. CONCLUSIONS: In an in vivo model of pneumonia developing shock, IgM-enriched immunoglobulins administered as rescue treatment enhance the anti-inflammatory response by increasing blood levels of IL-10 and reducing TNF-α in BAL fluid.
Authors: Axel Nierhaus; Giorgio Berlot; Detlef Kindgen-Milles; Eckhard Müller; Massimo Girardis Journal: Ann Intensive Care Date: 2020-10-07 Impact factor: 6.925
Authors: Jeroen D Langereis; Stefanie S Henriet; Saskia Kuipers; Corry M R Weemaes; Mirjam van der Burg; Marien I de Jonge; Michiel van der Flier Journal: J Clin Immunol Date: 2018-01-15 Impact factor: 8.317