[The effect of interleukin-7 and interleukin-15 on the production of Th1 and Th2 cytokines by peripheral blood mononuclear cells from patients with tuberculosis].
OBJECTIVE
To investigate the effect of interleukin-7 and interleukin-15 on the production of Th1 cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and Th2 cytokines interleukin-4 (IL-4), IL-10 by peripheral blood mononuclear cells (PBMC) from patients with tuberculosis.


METHODS
Peripheral blood was obtained from 60 tuberculosis patients and 25 healthy controls with a positive tuberculin test. PBMCs were isolated by centrifugation on a Ficoll-hypaque density gradient. According to the different stimulators, each sample was divided into six groups: RPMI-1640 group, PPD group, PPD + IL-7 group, PPD + anti-IL-7 group, PPD + IL-15 group, and PPD + anti-IL-15 group. The samples were cultured for 72 h and the supernatants were collected. The levels of IFN-gamma, TNF-alpha, IL-4 and IL-10 in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Compared with the PPD group, IL-7 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (157 +/- 74) ng/L, (460 +/- 128) ng/L to (887 +/- 242) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (31 +/- 9) ng/L, (153 +/- 40) ng/L to (112 +/- 32) ng/L, respectively]; IL-7 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (292 +/- 92) ng/L, (1,203 +/- 390) ng/L to (1,722 +/- 503) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 11) ng/L, (135 +/- 37) ng/L to (96 +/- 36) ng/L, respectively]. IL-15 increased the production of IFN-gamma and TNF-alpha in the patients [(107 +/- 42) ng/L to (231 +/- 62) ng/L, (460 +/- 128) ng/L to (843 +/- 208) ng/L, respectively], but decreased the production of IL-4 and IL-10 [(58 +/- 15) ng/L to (37 +/- 9) ng/L, (153 +/- 40) ng/L to (116 +/- 41) ng/L, respectively]; IL-15 also increased the production of IFN-gamma and TNF-alpha in the healthy controls [(211 +/- 57) ng/L to (343 +/- 108) ng/L, (1,203 +/- 390) ng/L to (1,468 +/- 235) ng/L, respectively], and decreased the production of IL-4 and IL-10 [(43 +/- 13) ng/L to (36 +/- 8) ng/L, (135 +/- 37) ng/L to (90 +/- 35) ng/L , respectively]. Anti-IL-7 and anti-IL-15 decreased the production of IFN-gamma and TNF-alpha, but increased the production of IL-4 and IL-10. The levels of IFN-gamma and TNF-alpha were lower in tuberculosis patients than those in the healthy controls (P < 0.05). The levels of IL-4 and IL-10 were not different between the two groups (P > 0.05).


CONCLUSIONS
IL-7 and IL-15 could affect the balance between Th1 and Th2 cytokines by inducing IFN-gamma and TNF-alpha production and inhibiting IL-4 and IL-10 expression. It is suggested that IL-7 and IL-15 may enhance the defense against infection of tuberculosis, and therefore may be useful for the treatment of the disease.
Yang
Xiao-min
XM
Department of Respiratory Medicine, Affiliated Hospital of Zunyi Medical College, Guizhou 563003, China.
Dong
De-qiong
DQ
Li
Chang
C
Yang
Yu-hao
YH
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D019409:Interleukin-15; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma