Abstract
Differences in the inflammatory response and prognosis of cryptogenic fibrosing alveolitis (CFA) and that associated with systemic sclerosis (FASSc) are beginning to emerge. It is hypothesized that these differences may be reflected in a distinct pattern of T-helper (Th)-1 and Th-2-type cytokines. Open lung biopsies were obtained from clinically well-documented cases of CFA and FASSc and, as a control, compared with grossly and histologically normal parenchyma obtained from smokers whose lungs were resected for cancer (n=5 in each group). In situ hybridization (ISH) was applied to the samples using anti-sense and sense 35S-labelled riboprobes to detect messenger ribonucleic acid (mRNA) for interleukins (IL)-2, IL-4, IL-5 and interferon (IFN)-gamma. Between 52-91% of cells expressing the cytokines studied were present in the alveolar interstitium rather than in lumenal cells or the alveolar epithelial lining. The highest values for all four cytokines were present in the patients with FASSc, i.e., 22-39 ISH positive cells x mm(-2) alveolar tissue compared with 1-19 cells x mm(-2) and 4-5 cell x mm(-2) in CFA and control subjects, respectively. Whereas the proportions of the four cytokines in FASSc were similar to the control subjects, IL-4 and IL-5 predominated significantly in CFA (p<0.001). For example, the ratio of IL-5 to IFN-gamma was 22:1 in CFA, significantly higher than in the cases with FASSc (2:1) or the control subjects (4:1) (p<0.05). In conclusion, cryptogenic fibrosing alveolitis is an inflammatory condition which is characterized, like asthma, by a predominance of gene expression for T-helper-2-type regulatory cytokines, whereas cryptogenic fibrosing alveolitis associated with systemic sclerosis appears to have a distinct mixed T-helper-1/T-helper-2 functional phenotype and a greater number of cells expressing each of these pro-inflammatory cytokines.
