Modulation of cytokines and chemokines, limited pulmonary vascular bed permeability, and prevention of septicemia and death with ceftriaxone and interleukin-10 in pneumococcal pneumonia.
Interleukin (IL)-10 is a biologically active anti-inflammatory and immunomodulatory cytokine. The respective effects or combined effect of ceftriaxone (Ctri) and IL-10 on host response was studied in a mouse model of lethal pneumococcal pneumonia. A once daily intraperitoneal (ip) injection of IL-10 (1 microg/mouse) for 2 days did not affect inflammation but accelerated bacterial dissemination to the bloodstream. Of mice treated with 1 ip 20 mg/kg Ctri injection, 40% developed septicemia, and only 52% survived. However, the addition of IL-10 to Ctri enhanced bacterial clearance, prevented septicemia, and yielded a 95% survival rate (P<.001). This approach also significantly (P<.05) decreased IL-1beta, IL-6, macrophage inflammatory protein-2, and myeloperoxidase levels in lungs and the production of nitric oxide in bronchoalveolar lavage fluid. Furthermore, Ctri plus IL-10 significantly (P<.05) reduced pulmonary vascular leakage and the appearance of red blood cells in alveoli. These data indicate a beneficial role for IL-10 as an adjunctive therapy to antibiotics against pneumococcal pneumonia.
Wang
E
E
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Département de Microbiologie, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, Canada.
Simard
M
M
Ouellet
N
N
Bergeron
Y
Y
Beauchamp
D
D
Bergeron
M G
MG
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002443:Ceftriaxone / Q000627:therapeutic use*; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000517:prevention & control*; D015996:Survival Rate
D018925:Chemokines; D016207:Cytokines; D016753:Interleukin-10; D002443:Ceftriaxone