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 immunomo dulatory cytokine. The respective effects or combined effect of ceftriaxone (Ctri) and IL-10 on host response was studied in a mouse model of lethal p neumococcal pneumonia. A once daily intraperitoneal (ip) injection of IL-10 (1 mu g/mouse) for 2 days did not affect inflammation but accelerated bact erial dissemination to the bloodstream of mice treated with 1 ip 20 mg/kg C tri injection, 40% developed septicemia, and only 52% survived. However, th e addition of IL-10 to Ctri enhanced bacterial clearance, prevented septice mia, and yielded a 95% survival rate (P < .001). This approach also signifi cantly (P < .05) decreased IL-1 beta, 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 blo od cells in alveoli, These data indicate a beneficial role for IL-10 as an adjunctive therapy to antibiotics against pneumococcal pneumonia.