The anti-inflammatory effects of corticosteroids are well known for their genomic mechanism producing biological actions. After the corticosteroids form complexes with glucocorticoid receptors (GCRs) inside the cytoplasm, the complexes translocate to the nucleus and bind to glucocorticoid-response elements on DNA. Once GCRs that had translocated into the nucleus bind to negative glucocorticoid-response element, the mRNA transcription of various cytokines involved in inflammation is inhibited. On the other hand, when GCRs translocate into the nucleus and bind to positive glucocorticoid-response element on DNA, the mRNA transcription of anti-inflammatory proteins is upregulated. The binding of transcription factors including nuclear factor-κB and AP-1 to DNA is inhibited, resulting in interference of cytokine production [16]. The amount of corticosteroid that would saturate corticosteroid receptors in an adult human is approximately 60 mg of prednisolone, although there are individual differences. In contrast, high-dose corticosteroid therapy is thought to act through a non-corticosteroid receptor-mediated mechanism, so-called non-genomic mechanism [17], which is entirely different from the genomic mechanism and has an onset of effect between a few seconds and a few minutes. Although the details are unknown at this time, there are two kinds of non-genomic mechanisms: nonspecific effects that directly act on cell membrane fluidity and specific effects that act on a specific receptor. Corticosteroid pulse therapy can be expected to have stronger genomic and non-genomic effects and have an impact on inflammatory cells, alveolar epithelial cells, T lymphocytes, vascular endothelial cells, etc. [18, 19]. Meanwhile, because corticosteroids do not inhibit the production of basic fibroblast growth factor and transforming growth factor-β (TGF-β) in bleomycin-induced murine pulmonary fibrosis [20], they have no antifibrotic actions. The following side effects of corticosteroids are important: diseases induced by infectious diseases (particularly tuberculosis, fungus, cytomegalovirus, Pneumocystis pneumonia, etc.), peptic ulcer, diabetes, mental deterioration, hypertension, secondary adrenocortical insufficiency, osteoporosis, aseptic necrosis of the femur and others, myopathy, glaucoma, cataract, thrombosis, endocrine abnormality, and so on. Because the above major side effects influence disease prognosis, whether the therapeutic effect is beneficial to the patient or not needs to be carefully pondered when such a side effect occurs. In addition, a decision must be made as to whether patients will continue the therapy with corticosteroid, reduce the dose, or discontinue this therapy. When a corticosteroid is administered for a long period of time, the combined treatment of sulfamethoxazole and trimethoprim is necessary to prevent Pneumocystis pneumonia. Because postmenopausal women and elderly people are vulnerable to the development of osteoporosis and compressed fracture, a medication such as bisphosphonate is also required. In contrast, minor side effects of corticosteroid administration include hirsutism, acne, moon-shaped face, extravasation of blood into the skin, purpura, and so on, but these side effects are sometimes not severe, and the physician may not recommend reducing the dose or discontinuing the drug.

Generally, an immunosuppressant is used for the treatment of various interstitial pneumonias other than IPF in the following cases: patients who have no response to corticosteroids, those who experienced severe side effects of corticosteroid, and those who are at high risk of developing side effects with corticosteroid. In the United States and Europe, cyclophosphamide and azathioprine are often used for treatment, but cyclosporine A is also used in Japan.