Inflammatory ctokines and nitric oxide in children with sepsis and septic shock

The objectives of the present study were to study the role played by plasma pro-inflammatory cytokine interleukin-6 [IL-6]; anti-inflammatory cytokine interleukin-10 [IL-10] and nitric oxide [NO] in the pathogenesis of pediatric sepsis and sepsis-related cardiovascular dysfunction; multiple organ dysfunctions and non-survival. Twenty-five patients with sepsis and 20 matched controls were enrolled. Patients were subdivided into three groups according to the severity of sepsis illness; uncomplicated sepsis[n,5]; sepsis syndrome[n,10] and septic shock [n,10]. The following daily measures were done during the three study days period: i] Determination of plasma levels of IL-6; IL-10 and NO metabolites, nitrite plus nitrate [NO[2]/NO[3]]; ii] Echocardiographic evaluation of cardiovascular functions by determining cardiac index[CI], left ventricular ejection fraction[LVEF] and end-diastolic volume index[EDVI] and iii] Determination of Organ Dysfunction Index [ODI] score. Follow-up for hospital mortality was also recorded. Results of the study showed that [I] In uncomplicated sepsis: Throughout the three sepsis days, plasma IL-6 showed significant increased levels that correlated positively with a simultaneous significant increased levels of IL-10; whereas plasma NO[2]/NO[3] levels were comparable with controls. ODI score was nil and no mortality reported [II] Throughout the three study days in sepsis syndrome group and early in septic shock: plasma IL-6 levels were significantly increased Vs uncomplicated sepsis group, accompanied by significantly reduced levels of IL-10; significant increased levels of NO[2]/NO[3] and significant rise of ODI score. Plasma IL-6 correlated positively with plasma NO[2]/NO[3] and both parameters correlated positively with ODI scores[III] Late in septic shock: plasma NO[2]/NO[3] levels were significantly increased Vs sepsis syndrome and early septic shock patients. This was accompanied with significantly reduced IL-6 and significantly increased IL-10 levels. In addition, significant drop of LVEF; significant rise of EDVI; significant rise of ODI score and 60% mortality were noted. Plasma NO[2]/NO[3] showed the only significant correlation with the severity of hypotension as well as with echocardiographic indices of cardiovascular dysfunction. Plasma IL-6, IL-10 and NO[2]/NO[3] correlated positively with ODI score. Admission plasma IL-6; IL-10 late in septic shock and plasma NO[2]/NO[3] at any time of septic shock showed significantly elevated levels in non-survivors Vs survivors. In i] The data of the current study suggested activation of proinflammatory cytokine - nitric oxide pathway in children with sepsis syndrome and septic shock that correlated significantly with the associated cardiovascular dysfunctions, multiple organ dysfunctions and non-survival. ii] Proinflammatory cytokines - nitric oxide activation probably plays a pivotal role in the pathogenesis of pediatric sepsis and may strengthen the argument for cytokines - NO modulation as a treatment for critically-ill children with sepsis; iii] Also the current data highlight the role of IL-10 in down regulating proinflammatory cytokines - nitric oxide activation in uncomplicated sepsis and opened the door for future therapeutic trials of IL-10 therapy in pediatric sepsis