[Preliminary study on effect of pentoxifylline in treatment of extrinsic allergic alveolitis].
OBJECTIVE
Pentoxifylline (POF) is a well established drug with haemorrheological properties. Various evidence suggests an additional therapeutic potential in regard to inflammation and immunomodulation. Extrinsic allergic alveolitis (EAA) is a granulomatous disease which is driven by T cell and alveolar macrophage (AM) derived cytokines. To investigate the effects of POF on the production of tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and the soluble TNF receptors (sTNFR1 and sTNFR2) from AM in EAA, also in comparison with dexamethasone (DEX).


METHODS
AM from 9 patients with EAA were cultured for 24 h with 10% RPMI medium alone, or with lipopolysaccharide (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 spontaneous TNFalpha and IL-10 release from AM in EAA (P < 0.001 and P < 0.05). The spontaneous production of other cytokines was unaffected by POF at all tested concentrations. DEX inhibited only the spontaneous release of TNFalpha significantly (P < 0.05). POF and DEX also inhibited the LPS-stimulated production of all cytokines except of IL-1beta and sTNFR1 (P < 0.001 or P < 0.01 or P < 0.05).


CONCLUSIONS
Our results may be the basis for clinical trials to evaluate the role of POF as an immunotherapeutic agent in the treatment of EAA.
Tong
Zhao-hui
ZH
Beijing Chao Yang Hospital-Beijing Institute of Respiratory Medicine, Beijing 100020, China.
Chen
Bao-min
BM
Dai
Hua-ping
HP
Wang
Chen
C
Guzman
Josune
J
Costabel
Ulrich
U
D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007378:Interleukins / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D007378:Interleukins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline