Investigators found increased transforming growth factor-β (TGF-β) pathway activity in the lung tissue of people with idiopathic pulmonary fibrosis (IPF) corresponded to lower levels of interleukin-22 (IL-22). Lower expression of IL-22 likewise corresponded with more severe pulmonary fibrosis.
TGF-β1 plays a crucial role in the development and progression of IPF by directly activating decapentaplegic signaling, which promotes profibrotic gene expression.
Researchers at the Nanjing Drum Tower Hospital and Wuxi People’s Hospital at Nanjing Medical University in China collected venous blood samples from 24 patients with IPF (21 males and 3 females) and 16 healthy volunteers (12 males and 4 females). They also injected mice with either 50 µl of normal saline or 5 mg/kg of bleomycin (BLM) to induce lung fibrosis.
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Chest high-resolution computed tomography allowed for assessment of the presence and extent of opacity, consolidation, reticulation, emphysema, honeycombing, and traction bronchiectasis. The researchers classified the degree of abnormalities using a 4-point scale.
Read more about IPF etiology
Investigators performed histopathological analyses of lung biopsies from the patients with IPF and the mice using hematoxylin and eosin and Masson’s trichrome staining to determine alveolitis and fibrosis scores. They determined serum plasma levels of IL-22 and conducted western blot analyses to detect IL-22 and TGF-β1 antibodies, among others.
Lastly, the investigators studied the in vitro effects of recombinant human IL-22 and/or recombinant human TGF-β1 treatment on 4 different cell cultures. They also treated the mice with BLM-induced IPF using IL-22 augmentation via intranasal instillation, which demonstrated efficacy in slowing the rates of alveolitis and fibrosis.
The in vitro human studies indicated that IL-22 augmentation treatment inhibited TGF-β1 signaling by repressing gene markers that correlated with IPF pathogenesis. Findings from the in vivo mouse model study confirmed that fibrotic exacerbation occurred due to a lack of IL-22 signaling, which amplified the TGF-β1 pathway.
Due to the scarcity of effective treatments for IPF, the authors suggest that “IL-22 augmentation may be a promising approach to treat IPF,” as “both in vitro and in vivo studies have further demonstrated . . . the protective function of IL-22 signaling.”
Reference
Gu P, Wang D, Zhang J, et al. Protective function of interleukin-22 in pulmonary fibrosis. Clin Transl Med. 2021;11(8):e509. doi:10.1002/ctm2.509
