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, pulmonary failure and death. The etiology of the disease is unknown, but the pathogenesis is believed to involve a persistent immunological reaction 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 sites of inflammation by a range of cell types. Patterns of cytokine reproduction by inflammatory cells are recognized to be associated with different 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 have studied cytokine expression in the intestinal inflammatory cell infiltrate in lung tissue from patients with CFA using mRNA in situ hybridization and immunohistochemistry. Our results show that while there is evidence for both a type 1 (characterized by interferon-gamma (IFN-gamma) 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 evidence suggests that IL-4 and IFN-gamma may be important regulatory factors for pulmonary fibroblasts. The relative paucity of IFN-gamma may contribute to the excessive fibroblast activation, deposition of collagen and scar formation that occurs in CFA.