EOSINOPHIL EXPRESSION OF TRANSFORMING-GROWTH-FACTOR-BETA AND ITS RECEPTORS IN NASAL POLYPOSIS - ROLE OF THE CYTOKINES IN THIS DISEASE PROCESS

Purpose: Nasal polyposis (NP) is characterized by an increase in infla mmatory processes including fibrosis. Because transforming growth fact or beta (TGF-beta) has been proven to induce fibrosis, we hypothesize that TGF-beta and its receptors ire present in NP and influence polyp development. Materials and Methods: To test this hypothesis, we evalua ted distribution (immunohistochemistry) of TGF-beta isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) and its receptors [(TGF-beta(RI) & TGF -beta(RII)] in NP from 36 NP patients and in five normal sinus tissue specimens obtained from septoplasty/inferior turbinectomy. Tissue leve ls of TGF-beta 1 and TGF-beta 2 levels were determined by enzyme-linke d immunosorbent assay (ELISA) and protein content was determined by Bi o Rad assay (Bio Rad, Richmond, CA). All tissue levels of TGF-beta wer e normalized and expressed as pg of TGF-beta per mg of total protein ( pg/mg TP). Results: Immunohistochemical studies showed eosinophils as the major cells positively staining for TGF-beta 1, TGF-beta 2, TGF-be ta 3, TGF-beta(RI), and TGF-beta. In fibrotic sections, increased stai ning of eosinophils, fibroblasts, and mononuclear cells was found for all three isoforms and both receptors. Evaluation of tissue levels ind icated mean levels for TGF-beta 1 in the NP were 11.64 +/- 22.12 pg/mg TP versus normal control mean 44.36 +/- 22.12 pg/mg TP. TGF-beta 2 me an levels were 11.46 +/- 23.73 pg/mg TP versus normal control mean of 2.03 +/- 1.13 pg/mg TP. NP showed decreased expression of TGF-beta 1 a nd enhanced expression of TGF-beta 2 isoforms with presence of their r eceptors. Higher levels of TGF-beta 2 correlated with an increase in p revious polypectomies perhaps indicative of severity oi disease (P les s than or equal to .0001). Conclusion: Our studies show the presence o f the TGF-beta isoforms and receptors in NP tissue. The results suppor t our hypothesis that the eosinophil continues to be a pivotal inflamm atory cell in NP, a differential regulation may govern the activity of TGF-beta in NP, and hence, the TGF-beta family of cytokines and recep tors likely play a key role in controlling NP formation. Copyright (C) 1997 by W.B. Saunders Company.