Cytokine Functions (7)
Th1 cytokines (e.g., interleukin [IL]-2 and interferon gamma):
- Promote cell-mediated immunity
- Remove cellular antigens
- Decrease fibroblast procollagen mRNA, fibroblast proliferation, and fibroblast-mediated angiogenesis
- Down-regulate transforming growth factor beta (TGF-ß)
The net effect of a predominantly Th1 response is tissue restoration.
Th2 cytokines (including IL-4 and IL-13):
- Promote humoral immunity
- Produce antibody responses that can lead to fibroblast activation and fibrosis
The net effect of a predominantly Th2 response is fibrosis.
In IPF, one proposal is that the resolution phase is marked by a persistent imbalance between Th1 and Th2 cytokines (7). As Th2 cytokines become more prevalent, transforming growth factor beta (TGF-ß) and other cytokine levels rise, causing fibroproliferation and excessive collagen accumulation (7). The increased levels of Th2 vs. Th1 cytokines in the lungs is thought to be one mechanism behind the progression of pulmonary fibrosis (7). In addition, IPF is characterized by fibroblast/myofibroblast migration and proliferation to sites of injury, decreased myofibroblast apoptosis, and increased activity of, and response to, fibrogenic cytokines such as transforming growth factor beta-1, connective tissue growth factor, endothelin-1, tumor necrosis factor alpha, platelet-derived growth factor, and insulin-like growth factor (8). Also, there appears to be failure of alveolar reepithelialization and a failure to turn off collagen proliferation, as well as a failure to break down collagen by naturally occurring metalloproteinases. Exactly what sets these abnormal tissue-repairv processes in motion is unclear, although in some cases genetic factors seem to play a role (1).
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