Hypersensitivity pneumonitis (HP) is categorized as a Type-1 helper (Th1) disease. The resulting granuloma formation is dependent on T cells and the Th1 cytokine interferon (IFN)-γ. In experimental setting, the production of IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG), IFN-inducible T-cell-alpha chemoattractant (I-TAC), has been shown (in mice exposed to the particulate antigens that cause HP) during the development of HP. The production of these chemokines was associated with an influx of chemokine (C-X-C motif) receptor (CXCR)3 CXCR3(+)/CD4(+) T cells into lungs. This suggests that IFN-γ mediates the recruitment of CXCR3(+)/CD4(+) T cells into the lung via the production of IP-10, MIG, and I-TAC, resulting in granuloma formation. In humans it has been shown that lymphocytes infiltrating lung biopsies are CD8 T cells for CXCR3. Furthermore, the T cells accumulating in the bronchoalveolar lavage (BAL) of HP were CXCR3(+)/IFN-γ(+) type 1 CD8(+) T cells (Tc1) exhibiting a strong in vitro migratory capability in response to IP-10. Alveolar macrophages express and secrete, in response to IFN-γ, high levels of IP-10, capable of inducing chemotaxis of the CXCR3(+) T-cell line. High levels of CXCR3 ligands were shown in the fluid of the BAL in HP patients. These data confirm that IFN-γ mediates the recruitment of lymphocytes into the lung via production of IP-10, resulting in Tc1-cell alveolitis and granuloma formation. It has been suggested that differences in the expression of CXC chemokines and Th1 cytokines may contribute to different immunopathogenesis, clinical course and responsiveness to treatment of HP.
Keywords: Alpha-chemokines; Hypersensitivity pneumonitis; IP-10; Occupational hypersensitivity pneumonitis.