Innate immune responses to Stenotrophomonas maltophilia in immunocompromised pediatric patients and the effect of taurolidine.
BACKGROUND
Stenotrophomonas maltophilia is an emerging pathogen causing invasive infections in immunocompromised pediatric patients, including neonates and pediatric oncology patients. Information on innate immune responses to S. maltophilia and its potential modulation are scarce.


METHODS
We established an in vitro S. maltophilia whole blood sepsis model and studied the proinflammatory cytokine production of CD14-positive cells by flow cytometry. We compared the cytokine expression of term newborns (n = 13) and healthy adults (n = 10) and investigated in vitro responses of pediatric oncology patients after recovery from neutropenia (n = 10) with healthy adults (n = 10). We further evaluated the immunomodulatory role of the amino-acid derivative taurolidine in our in vitro sepsis model.


RESULTS
Proinflammatory cytokine responses to S. maltophilia were largely diminished in the neonatal population. No remarkable differences were noted for cytokine responses between pediatric oncology patients and healthy controls. Taurolidine inhibited immunoglobulin (IL)-6, IL-8 and tumor necrosis factor-alpha expression in a dose dependent-fashion in both, pediatric oncology patients and healthy controls.


CONCLUSIONS
Deficient immune responses to S. maltophilia require optimized prevention strategies against infection in immunocompromised patients, including neonates. Taurolidine may be an effective immunomodulatory agent in a clinical setting.
Department of Paediatrics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. haertel@paedia.ukl.mu-luebeck.de
Christoph
C
Härtel
Tasja
T
Scholz
Marie
M
Kuhn
Meike
M
Bendiks
Wolfgang
W
Göpel
Melchior
M
Lauten
Egbert
E
Herting
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007231:Infant, Newborn; D007962:Leukocytes / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008962:Models, Theoretical; D020615:Stenotrophomonas maltophilia / Q000276:immunology*; D013654:Taurine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013829:Thiadiazines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine