tacrolimus and Respiratory-Distress-Syndrome

Topics: Abatacept; Aged; Calcineurin Inhibitors; Drug Resistance; Drug Substitution; Fatal Outcome; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Respiratory Distress Syndrome; Risk Factors; Tacrolimus

Topics: Adrenal Cortex Hormones; Antibodies, Antinuclear; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Myography; Polymyositis; Respiration, Artificial; Respiratory Distress Syndrome; Syndrome; Tacrolimus

Polymyositis and interstitial lung diseases, predominantly nonspecific interstitial pneumonia (NSIP), are known to be frequent in antisynthetase syndrome, where anti-aminoacyl-tRNA synthetase antibodies are often identified. An unusual case of acute respiratory distress syndrome, secondary to such proven NSIP of cellular type with predominant CD8 lymphocytes, is described herein. The patient described in the present case study initially had a poor recovery with high dose of steroids, but this was followed by a good improvement after the prescription of tacrolimus and a low dose of prednisone. A precise diagnosis in similar circumstances may be life-saving, allowing the successful application of new immunosuppressants.

Topics: Antibodies, Antinuclear; Autoantibodies; CD8-Positive T-Lymphocytes; Cyclosporine; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Middle Aged; Polymyositis; Respiratory Distress Syndrome; Syndrome; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.

Topics: Animals; Disease Models, Animal; Endotoxins; Humans; Leukocytes; Lung; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Sheep; Tacrolimus

The novel effects of FK506 on shock induced by lipopolysaccharide and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both 0.5 mg/kg of LPS and 30 microg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 microg/kg/h (low dose, n = 5), 8 microg/kg/h (medium dose, n = 5), and 25 microg/kg/h (high dose, n = 5) were administered. In the control group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed. FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA-induced physiological changes, and the survival rates were 80 and 100%, respectively. On the other hand, in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock.

Topics: Animals; Dogs; Hemodynamics; Immunosuppressive Agents; Organ Size; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Shock, Septic; Survival Rate; Tacrolimus

A 40-year-old man with chronic myelogenous leukemia in chronic phase received an allogeneic marrow graft from his HLA identical brother. He was conditioned with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was attempted with cyclosporine A (CYA) and methotrexate. On day 30, weight gain, ascites and hepatomegaly developed in addition to an elevation of total bilirubin (TB). He was diagnosed as having veno-occlusive disease (VOD) and treated conservatively. The TB level increased up to 20.1 mg/dl on day 66, then reduced to 2.1 mg/dl on day 129. By that time ascites and hepatomegaly also had completely resolved. However, on day 134. The TB level started to increase again, when the lesions of chronic GVHD were observed in the eye, the mouth, and the skin. CYA was started on day 142, and FK506 was substituted for CYA on day 161. Despite the improvement of oral and skin lesions, TB level continued to rise, and he died of respiratory failure due to ARDS on day 186. Autopsy revealed both acute and old hepatic VOD lesions, suggesting the occurrence of late-onset VOD which probably contributed to the liver dysfunction observed after clinical resolution of the first episode of VOD.

Topics: Adult; Bone Marrow Transplantation; Busulfan; Chronic Disease; Cyclophosphamide; Cyclosporine; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Methotrexate; Recurrence; Respiratory Distress Syndrome; Tacrolimus