Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis children

Background: The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Ex uberant production of TNF-alpha contributes to overwhelming inflammatory re sponse and tissue damage. But, commonly, increase in TNF-alpha is counterba lanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, wh ich suppresses production of many activating and regulatory mediators. Aims: In the present study, the relationships between TNF-alpha and IL-10 i n the plasma of healthy schoolchildren and cystic fibrosis (CF) patients ha ve been investigated. Methods: Blood samples were obtained from 12 CF patients with chronic pulmo nary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. Results: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF -alpha /IL-10>1). In these subjects, a significant positive linear associat ion between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha /IL-10 ratios. In addition, a disappeara nce of correlation between the cytokine values was observed. Such disturban ce was related to exuberant elevation of the IL-10 levels after inoculation . On the contrary, in CF individuals, plasma cytokine values remained in st rong linear association independently of TNF-alpha or IL-10 predominance. N o spikes in the plasma levels of IL-10 in CF patients during a 6-month obse rvation period have been revealed. Conclusions: There were no fundamental differences between CF and healthy c hildren in the regulation of TNF-alpha and IL-10 secretion. Thus, immune qu iescence seemed to be associated with the predominance of TNF-alpha, wherea s immune disturbance was characterized by IL-10 superiority. The only abnor mality that was found in CF patients consisted of their inability to produc e unlimitedly IL-10 in response to antigen stimuli.