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 dexame thasone (Dex) are used in the treatment of asthma as anti-inflammatory agen ts. Objective: We investigated whether DSCG inhibited the expression of IL-5 an d 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 atop ic 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 De rmatophagoides antigen, then cultured for 48 hours. The supernatant was col lected 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 transcr iptase-polymerase chain reaction (RT-PCR). Results: Tumor necrosis factor-alpha protein reached a peak level at 4 hour s (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 obs erved at 24 hours (150.29 +/- 19.12 pg/mL). Dex decreased IL-5 protein to 2 8.57 +/- 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, Conclusion: Our results showed that DSCG significantly inhibited IL-5 and T NF-alpha production by human lung specimens, suggesting that it acts as an antiinflammatory agent.