Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis

Abstract

Interstitial pneumonitis (IP) is the most frequent and serious pulmonary involvement in patients with dermatomyositis (DM)/polymyositis (PM) [1][2][3][4][5][6][7][8]. In one study representing the largest series of autopsy cases with DM/PM, the mean survival of patients with IP was shown to reduce to only 8 months after the onset of pulmonary symptoms [5]. We also showed that IP developed in 32% of 111 DM/PM patients and that 35% of DM/PM patients with IP died of respiratory failure in a year [8]. Moreover, it has been shown that 44-60% of IP in DM/PM, especially in DM, is resistant to high-dose corticosteroid therapy and the corticosteroid-resistant IP patients die of respiratory failure in a relatively short period [6][7][8]. Furthermore, we and others have recently shown that the corticosteroid-resistant IP is successfully treated with a T cell-specific immunosuppressant cyclosporin [8][9][10], suggesting that the activation of T cells is importantly involved in the development of corticosteroid-resistant IP in DM/PM. Therefore, in order to determine the difference in T cell activation states between corticosteroid-resistant and corticosteroidsensitive IP in DM/PM, we studied the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. Our results indicate that activated Th1-type pulmonary T cells are importantly involved in the development of corticosteroidresistant IP in DM/PM and that the increase in CD25 + CD8 + T cells in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM. 541 Activation of pulmonary T cells in corticosteroid- SUMMARYTo study the activation states and cytokine profiles of pulmonary T cells in corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. CD25 + CD4+ T cells in BALF were significantly increased in both corticosteroid-resistant and corticosteroidsensitive IP in DM/PM as compared with those in controls without IP. Furthermore, CD25 + CD4 + T cells in BALF were significantly more increased in corticosteroid-resistant IP than those in cortico teroidsensitive IP. Moreover, CD25+ CD8

Treatment of antisynthetase‐associated interstitial lung disease with tacrolimus

“…However, our data and those from previously published studies (19)(20)(21)(22)(23) suggest that a T cell inhibitor such as cyclosporine or tacrolimus may be effective in treating connective tissue disease-associated ILD.…”

“…Although the pathogenesis of myositis-associated ILD is unknown, a recent study indicated that activated Th1-type pulmonary T cells play an important role in the development of corticosteroid-resistant ILD in patients with PM and DM (23). These findings suggest that a T cell inhibitor, such as tacrolimus, may be of benefit in patients with interstitial pneumonitis.…”

Predictive Models of Clinical Improvement in Rituximab-Treated Myositis Patients Using Clinical Features, Autoantibodies, and Biomarkers

“…For example, expression of IL-18 at in muscle from patients with myositis has been associated with treatment-resistant disease [20]. Similarly, expression of Th1-associated cytokines has been associated with corticosteroid-resistant interstitial lung disease in both PM and DM [21]. Therefore, in our previous study we sought to examine the IFN regulated chemokine and cytokine profiles in the serum of rituximab-treated refractory myositis patients, and explore the impact of rituximab on these cytokine/chemokine profiles at 8 and 16 weeks after rituximab treatment [12].…”

Interstitial Lung Disease Associated with Clinically Amyopathic Dermatomyositis

“…www.intechopen.com 5.6 Characteristics of patients with interstitial lung disease in polymyositisdermatomyositis resistant to prednisolone and cyclosporine Cyclosporin binds to cyclophilin, then the complex inhibits calcineurin phosphatase and Tcell activation (Clipstone & Crabtree, 1992). Because activated T lymphocytes, in particular CD8 + T cells, may play essential roles in intestitial lung disease associated with PM-DM (Enomoto et al, 2003, Kourakata et al, 1999, Kurasawa et al, 2002, immunosuppressive therapy targeting CD8 + cells should be reasonable. However, CD4/8 ratio in bronchoalveolar lavage fluid was significantly increased in cyclosporine-resistant cases compared to alive ones.…”