INCREASED EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-6, PLATELET-DERIVED GROWTH FACTOR-B AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR MESSENGER-RNA IN CELLS OF BRONCHOALVEOLAR LAVAGE FLUIDSFROM PATIENTS WITH SARCOIDOSIS

Cytokines released from activated alveolar macrophages and T-lymphocyt es affect the accumulation of monocyte-macrophage-lineage cells and th erefore play an important role in the formation of sarcoid granuloma. Although it is likely that certain monokines and lymphokines are invol ved in the development of sarcoid granulomas, the evidence for this is not unequivocal. In an attempt to clear critical cytokines in the dev elopment and maintenance of sarcoid granuloma, we have measured the le vel of seven cytokine mRNA (TNF-alpha, IL-6, IL-8, TGF-beta, PDGF-B, l FN-gamma, and GM-CSF) in cells obtained by BAL from sarcoidosis patien ts and normal subjects. To detect cytokine mRNA, we employed a reverse transcription-polymerase chain reaction, We report that the levels of TNF-alpha, IL-6, PDGF-B and GM-CSF mRNA were significantly increased in BAL cells from the patients with pulmonary sarcoidosis compared to controls. No significant differences were observed in the mRNA express ion of IL-8, TGF-beta and IFN-gamma. A significant correlation of the expression of the mRNA levels of seven cytokines in the same patients with sarcoidosis was observed between IL-8 and TNF-alpha, PDGF-B, and IL-6, IL-8 and IL-6 and TFN-alpha and PDGF-B and IL-8. This finding in dicates that at least these four cytokines are involved in the cytokin e network at the local alveolar site of chronic granulomatous inflamma tion, This study adds a report to the literature that supports a role for cytokine, TNF-alpha, IL-6, PDGF and GM-CSF in particular, in the p romotion and maintenance of sarcoid granulomatous inflammation.