Th2-type cytokines and the Fas way to pulmonary fibrosis: Comment on the article by Atamas et al

Apoptosis, airway inflammation and anti‐asthma therapy: From immunobiology to clinical application

“…Airway remodelling has been also observed in several fibrotic syndromes, such as interstitial lung diseases, where Th2 cytokines may play a pro‐inflammatory role (Fig. 2) (39–41). Studies in humans and animal models of interstitial pneumonitis show that alveolar epithelial damage occurs first, and is followed by infiltration of B and T lymphocytes, polymorphonuclear leukocytes, plasma cells and macrophages, thus leading to final organization of alveolar exudate.…”

“…All these data shed light on the mechanisms through which Th2 cytokines may interfere with the resolution of the inflammatory process. Their anti‐apoptotic mechanism of action undoubtedly enhance the survival of infiltrating lymphocytes, granulocytes, plasma cells and macrophages, but a pro‐fibrotic activity because of prolonged fibroblast survival should also be considered as a major factor in airway inflammation and remodelling (41).…”

Biological effects of montelukast, a cysteinyl‐leukotriene receptor‐antagonist, on T lymphocytes

“…T‐helper type 2 (Th2)‐type cytokines are primarily involved in in vitro induction of Fas mRNA suppression in a dose‐dependent manner, which resembles what usually occurs in allergic inflammation in vivo [21]. Among 5‐lipoxygenase products, 5‐HETE [22] and LTB 4 [23] display an anti‐apoptotic activity on several cell types including leucocytes, a property that is also common to Th2‐type cytokines [24]. Thus, many cellular and soluble mediator loops seem to act synergistically in prolonging the survival of inflammatory cells.…”