Abstract
The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated. 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-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. 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 association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/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-alpha 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. There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, 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.
Highlights
Challenge with infectious agents or their products provoke early secretion of regulatory cytokines including tumor necrosis factor-a (TNF-a ) and interleukin-10 (IL-10)
We found a marked elevation in plasma cytokine concentrations in healthy individuals following rubella vaccination
Foey et al hypothesized that IL-10 production requires at least two signals; the first is provided by lipopolysaccharide, and the second by endogenous TNF-a and/or IL-1b
Summary
Challenge with infectious agents or their products provoke early secretion of regulatory cytokines including tumor necrosis factor-a (TNF-a ) and interleukin-10 (IL-10). These cytokines are produced by the activated macrophages and play opposite roles in both innate and specific immune response.[1,2] TNF-a upregulates production of other pro-inflammatory cytokines by the immune and nonimmune cells[3,4,5,6], augments leukocyte adhesion and promotes cell migration into the tissue space.[7] It facilitates antimicrobial activity of neutrophils and macrophages but, in addition, potentiates their tissue-damaging properties.[8] Overzealous production of the cytokine may have serious adverse consequences such as systemic inflammation and septic shock.[9,10] But, commonly, rapid increase inTNF-. Results: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-a over anti-inflammatory IL-10 (TNF-a /IL-10 > 1) In these subjects, a significant positive linear association between the cytokine values has been found. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli
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