Immunoreactive interleukin 4 and interferon-gamma expression by type II alveolar epithelial cells in interstitial lung disease

Cryptogenic fibrosing alveolitis (CFA), extrinsic allergic alveolitis (EAA) , and sarcoid are all immunologically mediated forms of interstitial lung d isease. In contrast to most patients with EAA and sarcoid, patients with CF A show relentless pulmonary fibrosis which is unresponsive to immunosuppres sive therapy. Previous studies have indicated a possible role for epithelia l-derived cytokines in the regulation of immunological and fibrotic respons es in the lung, This study has examined lung biopsy specimens from patients with CFA, EAA, and sarcoid for immunoreactive interleukin 4 (IL4) and inte rferon-gamma (INF gamma) expression by type II alveolar epithelial cells, a s these cytokines have been suggested to have in vitro stimulatory and inhi bitory effects on fibroblast function, In addition, mRNA in situ hybridizat ion was performed on the CFA lung biopsies to confirm transcription of thes e cytokine genes within the cells. The results show that type II epithelial cells in EAA and sarcoid show up-regulation of immunoreactivity for both I L4 and INF-gamma, but that in CFA only IL4 is detectable. The mRNA in situ: hybridization results indicate that this may represent post-transcriptiona l regulation of INF gamma, expression in CFA. These results are consistent with previous observations of a paucity of INF gamma and a predominantly ty pe II (Th2-like) pattern of immune response in patients with CFA and sugges t a possible imbalance of pro-fibrogenic cytokines in the distal lung of pa tients with this condition, compared with those with EAA or sarcoid. Copyri ght (C) 1999 John Wiley & Sons, Ltd.