Effects of sodium cromoglycate on cytokine production following antigen stimulation of a passively sensitized human lung model.
BACKGROUND
Interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-alpha) play key roles in bronchial asthma. Sodium cromoglycate (DSCG) and dexamethasone (Dex) are used in the treatment of asthma as anti-inflammatory agents.


OBJECTIVE
We investigated whether DSCG inhibited the expression of IL-5 and TNF-alpha mRNA and proteins from isolated human lungs, and compared these findings with those of Dex.


METHODS
Human lung specimens were passively sensitized with sera from atopic patients, then preincubated in the presence of DSCG (10(-3), 10(-4), 10(-5) M) or Dex (10(-6) M) for 2 hours. The specimens were stimulated with Dermatophagoides antigen, then cultured for 48 hours. The supernatant was collected 1, 2, 4, 8, 24, and 48 hours to measure IL-5 and TNF-alpha by enzyme-linked immunosorbent assay. mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR).


RESULTS
Tumor necrosis factor-alpha protein reached a peak level at 4 hours (156.57 +/- 18.29 pg/mL). Dex decreased TNF-alpha protein to 31.86 +/- 4.67 pg/mL (P < .001). There was also a decrease of TNF-alpha protein to 107.43 +/- 14.25 pg/mL by 10(-4) MD SCG (P < .001). Antigenic stimulation also increased the release of IL-5 protein at 4 hours and the peak level was observed at 24 hours (150.29 +/- 19.12 pg/mL). Dex decreased IL-5 protein to 28.57 +/- 5.27 pg/mL (P < .0001), 10(-4) M DSCG also decreased to 111.57 +/- 15.28 pg/mL (P < .05). RT-PCR analysis showed persistence of IL-5 and TNF-alpha mRNA expression from 1 to 24 hour after antigen stimulation. Dex but not DSCG inhibited IL-5 and TNF-alpha mRNA levels.


CONCLUSIONS
Our results showed that DSCG significantly inhibited IL-5 and TNF-alpha production by human lung specimens, suggesting that it acts as an anti-inflammatory agent.
Matsuo
N
N
The Second Department of Internal Medicine, Nagasaki University, School of Medicine, Japan.
Shimoda
T
T
Matsuse
H
H
Obase
Y
Y
Asai
S
S
Kohno
S
S
D000368:Aged; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007116:Immunization, Passive; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D018927:Anti-Asthmatic Agents; D015848:Interleukin-5; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D004205:Cromolyn Sodium