THE ROLE OF NEUTROPHILS IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS

Study objectives: The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial, The role of neutrophils in this i nflammatory lung disease, therefore, was evaluated in this study by ad ditional measures. Materials and methods: We performed BAL, in 22 pati ents with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung b iopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmoke rs. Elastase complexed to alpha-l-proteinase inhibitor (alpha(1)-PI) i n plasma and BALF was measured as a marker of elastase burden, and neu trophil distribution in 22 lung tissues was observed by immunohistoche mistry using antineutrophil elastase antibody, Results: Percent PMN an d absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=15); the plasma elastase-al pha(1)-PI complex value (mean+/-SE) of patients with IPF (668.5+/-112. 4 ng/mL) was significantly high as compared with that of normal nonsmo kers (130.3+/-21.3, p < 0.001). In addition, the PALE elastase-alpha(1 )-PI complex value (mean+/-SE) of patients with IPF was also significa ntly high (333.1+/-87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1+/-29.3 ng/mg albumin, p < 0.05). Immunohistochemistr y demonstrated considerable numbers of neutrophils infiltrating the lu ng parenchyma in biopsy specimens obtained by open lung biopsy. Conclu sions: These results suggested that although the neutrophil count in B ALF could not represent the distribution of neutrophil in the lung, hi gh levels of neutrophil elastase were demonstrated in lung parenchyma and also in both PALE and sera. Therefore, neutrophils might indeed pl ay an important role in the pathogenesis of IPF.