A TYPE-2 (TH2-LIKE) PATTERN OF IMMUNE-RESPONSE PREDOMINATES IN THE PULMONARY INTERSTITIUM OF PATIENTS WITH CRYPTOGENIC FIBROSING ALVEOLITIS(CFA)

CFA is an inflammatory condition of the lungs resulting in scarring, p ulmonary failure and death. The etiology of the disease is unknown, bu t the pathogenasis is believed to involve a persistent immunological r eaction to unidentified antigen in the lung resulting in tissue damage . Recent advances in our understanding of the immune system have shown that different patterns of stimulatory cytokines are produced at site s of inflammation by a range of cell types. Patterns of cytokine produ ction by inflammatory cells are recognized to be associated with diffe rent patterns of immunological response, and these have been described as type 1 (or Th1-like) and type 2 (or Th2-like) on this basis. We ha ve studied cytokine expression in the intestinal inflammatory cell inf iltrate in lung tissue from patients with CFA using mRNA in situ hybri dization and immunohistochemistry. Our results show that while there i s evidence for both a type 1 (characterized by interferon-gamma (IFN-g amma)) and type 2 (characterized by IL-4 and IL-5) response present in CFA, the type 2 (or Th2) pattern of cytokines appears to predominate. This would be consistent with a possible role for the humoral immune response in the pathogenesis of this condition. In addition, recent ev idence suggests that IL-4 and IFN-gamma may be important regulatory fa ctors for pulmonary fibroblasts. The relative paucity of IFN-gamma may contribute to the excessive fibroblast activation, deposition of coll agen and scar formation that occurs in CFA.