Background: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis. Methods: Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue. Results: Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-β₁, platelet derived growth factor-AB, and thrombin. Conclusions: A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-β₁, platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.

Activation of orbital fibroblasts resulting in excessive proliferation, cytokine and hyaluronan production and differentiation into adipocytes, is a main determinant of orbital tissue inflammation and tissue expansion in Graves' ophthalmopathy (GO). During the last years we have shown that the platelet-derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased in orbital tissue from GO patients with active and inactive disease. These PDGF isoforms exhibit the capacity to stimulate proliferation, hyaluronan and cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF-BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital fibroblasts, which enhances the orbital fibroblast activating capacity of the THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating effects, which is likely related to its ability to bind both the PDGF-receptor (PDGF-R)α and PDGF-Rβ chains. Thus the PDGF-system fulfills important roles in orbital fibroblast activation in both active and inactive GO, which supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine kinase inhibitors (TKIs) may be candidates to target PDGF signaling. Of several TKIs tested dasatinib exhibited the highest potency to block PDGF-R signaling in orbital fibroblasts and may represent a promising compound for the treatment of GO as it was effective at low dosage and is associated with less side effects compared to imatinib mesylate and nilotinib. In this review the contribution of PDGF to the pathophysiology of GO as well as therapeutic approaches to target this PDGF-system will be addressed.

Complex regional pain syndrome (CRPS) is characterized by continuous pain that is often accompanied by sensory, motor, vasomotor, sudomotor, and trophic disturbances. If left untreated, it can have a significant impact on the quality of life of patients. The diagnosis of CRPS is currently based on a set of relatively subjective clinical criteria: the New International Association for the Study of Pain clinical diagnostic criteria for CRPS. There are still no objective laboratory tests to diagnose CRPS and there is a great need for simple, objective, and easily measurable biomarkers in the diagnosis and management of this disease. In this review, we discuss the role of inflammation in the multi-mechanism pathophysiology of CRPS and highlight the application of potential biomarkers of inflammation in the diagnosis and management of this disease.