Circulating Cytokine Levels and Changes During the Treatment in Patients with Active Tuberculosis in Korea

Ryu, Yon Ju; Kim, Yun Jung; Kwon, Jung Mi; Na, Youn ju; Jung, Yu Jin; Seoh, Ju Young; Cheon, Seon Hee

Abstract

BACKGROUND: The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. METHOD: Serum interleukin-1 beta(IL-1 ), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-alpha), interferon-gamma(IFN-gamma) and transforming growth factor-beta(TGF-beta) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-alpha, IFN-gamma and TGF-beta levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment.
RESULTS
1) In sera of patients with active pulmonary tuberculosis(n=83), IL-1beta, IL-6(p<0.05), TNF-alpha, and IFN-gamma were elevated and TGF-beta was decreased comparing to control. IL-2, IL-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-alpha were elevated and TGF-beta was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-gamma level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 and TNF-alpha and between IL-12, IL-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-gamma was significantly decreased(p<0.05).
CONCLUSION
These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.