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

Abstract

Background: The balance between tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-α contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-α is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. Aims: In the present study, the relationships between TNF-α and IL-10 in the plasma of healthy schoolchildren and cystic fibrosis (CF) patients have been investigated. Methods: Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-α 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-α over anti-inflammatory IL-10 (TNF-α/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-α/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-α or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed. Conclusions: There were no fundamental differences between CF and healthy children in the regulation of TNF-α and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-α, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.