tacrolimus and Leukocytosis

Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss.. Case series and review of the literature.. We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy.. Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.

Topics: Aged; Bone Marrow Transplantation; Cerebrospinal Fluid; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukocytosis; Lymphocytes; Magnetic Resonance Imaging; Male; Middle Aged; Optic Disk; Optic Nerve Diseases; Tacrolimus; Visual Acuity; Visual Field Tests; Visual Fields

Stiffness and cytokine in blood levels show 24-h rhythms in rheumatoid arthritis (RA) patients. We previously revealed that higher therapeutic effects were obtained in RA patients and RA model animals when the dosing time of methotrexate was chosen according to the 24-h rhythms to cytokine. In this study, we examined whether a dosing time-dependency of the therapeutic effect of tacrolimus (TAC) could be detected in collagen-induced arthritis (CIA) and MRL/lpr mice. To measure the levels of cytokines and serum amyloid A (SAA), blood was collected from CIA mice at different times. TAC was administered at two different dosing times based on these findings and its effects on arthritis and toxicity were examined. Plasma tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and SAA concentrations showed obvious 24-h rhythms with higher levels during the light phase and lower levels during the dark phase after RA crisis. The arthritis score and leukocyte counts were significantly lower in the group treated at 2 h after the light was turned on (HALO) than in the control and 14 HALO-treated groups. Our findings suggest that choosing an optimal dosing time could lead to the effective treatment of RA by TAC.

Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Collagen Type II; Drug Chronotherapy; Immunosuppressive Agents; Interleukin-6; Leukocyte Count; Leukocytosis; Male; Mice; Mice, Inbred DBA; Mice, Inbred ICR; Mice, Inbred MRL lpr; Renal Insufficiency; Serum Amyloid A Protein; Severity of Illness Index; Tacrolimus; Tumor Necrosis Factor-alpha

Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease.. Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days.. Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1beta, TNF-alpha and IL-6.. The effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease.

Topics: Alveolar Bone Loss; Animals; Calcineurin Inhibitors; Dinoprostone; Disease Models, Animal; Gingiva; Immunologic Factors; Immunosuppressive Agents; Interleukin-1beta; Interleukin-6; Leukocyte Count; Leukocytosis; Male; Periodontitis; Peroxidase; Rats; Rats, Wistar; Tacrolimus; Time Factors; Tumor Necrosis Factor-alpha

Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD) prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC transplants but in none of 11 patients receiving autologous HSC transplants. Of the 12 patients with CSF pleocytosis, only one patient developed leukoencephalopathy later. There was a correlation between CSF cell numbers and trough levels of CSA but not with those of FK506. In patients receiving allogeneic HSC transplants, CSF pleocytosis may be relatively common and may reflect neurologic damage associated with calcineurin inhibitors.

Topics: Adult; Cell Count; Cerebrospinal Fluid; Cyclosporine; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukocytosis; Male; Premedication; Tacrolimus; Transplantation, Autologous; Transplantation, Homologous