[Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylline].
OBJECTIVE
Pentoxifylline (POF) has recently been shown to suppress the cytokine production from lipopolysaccharide (LPS) stimulated monocytes/alveolar macrophages (AM). Sarcoidosis is a granulomatous disease which is driven by the action of tumor necrosis factor (TNF-alpha) and other proinflammatory cytokines. It was investigated that the effects of POF on the production of TNF-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and the soluble TNF-alpha receptors (sTNFR-1 and sTNFR-2) from AM in sarcoidosis, as comparison to dexamethasone (DEX).


METHODS
AM from 14 patients with active pulmonary sarcoidosis were cultured for 24 h with RPMI medium alone, or with LPS (100 micro g/L), and with POF at concentrations of 0.01 mmol/L, 0.1 mmol/L and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analysed by ELISA.


RESULTS
POF induced a dose dependent suppression of the spontaneous TNF-alpha release from AM in sarcoidosis (P < 0.001), while the spontaneous release of other cytokines was unaffected by POF at all tested concentrations, but a trend for the inhibition of IL-10 production was found (P = 0.092). DEX 0.1 mmol/L inhibited the spontaneous release of TNF-alpha, sTNFR-2, IL-1beta and IL-10 (P < 0.001 or < 0.05 or <0.01). POF also suppressed the production of these LPS-stimulated cytokines except of sTNFR-1 (P < 0.05 or < 0.001). Similar to POF, DEX (0.1 mmol/L) inhibited the production of these LPS-stimulated cytokines (P < 0.05 or < 0.001), but not of sTNFR-1 and IL-1beta.


CONCLUSIONS
Compared with DEX, POF may improve the therapy of sarcoidosis by either sparing or replacing corticosteroids. However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases needs to be determined in further clinical trials.
Tong
Zhao-hui
ZH
Beijing Chaoyang Hospital-Beijing Institute of Respiratory Medicine, Beijing 100020, China.
Dai
Hua-ping
HP
Chen
Bao-min
BM
Wang
Chen
C
Guzman
Josune
J
Costabel
Ulrich
U
D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology
D016207:Cytokines; D008070:Lipopolysaccharides; D003907:Dexamethasone; D010431:Pentoxifylline