Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis - A quantitative study ofopen lung biopsies

Differences in the inflammatory response and prognosis of cryptogenic fibro sing alveolitis (CFA) and that associated with systemic sclerosis (FASSc) a re beginning to emerge. It is hypothesized that these differences may be re flected 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 C FA and FASSc and, as a control, compared with grossly and histologically no rmal 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 S-35-labelled riboprobes to detect messenger ri bonucleic acid (mRNA) for interleukins (IL)-2, IL-4, IL-5 and interferon (I FN)-gamma. Between 52-91% of cells expressing the cytokines studied were present in th e alveolar interstitium rather than in lumenal cells or the alveolar epithe lial lining. The highest values for all four cytokines were present in the patients with FASSc, ie., 22-39 ISH positive cells.mm(-2) alveolar tissue c ompared with 1-19 cells.mm(-2) and 4-5 cells.mm(-2) in CFA and control subj ects, respectively. Whereas the proportions of the four cytokines in FASSc were similar to the control subjects, IL-4 and IL-5 predominated significan tly 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 cont rol subjects (4:1) (p<0.05). In conclusion, cryptogenic fibrosing alveolitis is an inflammatory conditio n which is characterized, like asthma, by a predominance of gene expression for T-helper-2-type regulatory cytokines, whereas cryptogenic fibrosing al veolitis associated with systemic sclerosis appears to have a distinct mixe d T-helper-1/T-helper-2 functional phenotype and a greater number of cells expressing each of these pro-inflammatory cytokines.