thymic-factor--circulating and Graft-vs-Host-Disease

The effects of a thymic hormone (Facteur thymique serique; FTS) on renal reactive oxygen species-scavenging enzymes or substances in heminephrectomized rats with and without tacrolimus-induced nephrotoxicity were studied. Rats received both oral dose of tacrolimus (5 mg/kg/day) and subcutaneous administration of three dosages of FTS (5, 50, and 250 microg/kg/day) over 28 days (Group A). In Group B, they received three dosages of FTS alone (0.5, 5, and 50 microg/kg/day) or FTS 50 microg/kg/day with tacrolimus over 28 days. Each dose of FTS (Group A) partially elevated renal creatinine clearances. Tacrolimus enhanced renal glutathione reductase (GSH-R) activities and glutathione (GSH) and depressed catalase (CAT) activities. FTS increased GSH levels and GSH-R activities. Although FTS alone did not change CAT activities, CAT activities recovered as a result of concomitant use of FTS (Groups A and B). A significant positive correlation was found between CAT activity and creatinine clearance. These findings suggest that FTS is useful for the prevention of tacrolimus-induced nephrotoxicity, and that the increase of renal CAT activity in the defense mechanism of FTS might be important for cell protection against active oxygen species.

Topics: Animals; Catalase; Glutathione; Glutathione Peroxidase; Graft vs Host Disease; Immunosuppressive Agents; Kidney; Male; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Tacrolimus; Thymic Factor, Circulating

We have previously reported that a nonapeptide thymic hormone, facteur thymique serique (FTS), is involved in the differentiation and activation of intestinal intraepithelial lymphocytes (i-IEL) in mice. In this study, we examined the effect of FTS treatment on enteropathy in a murine model for acute graft-vs.-host disease (GVHD) induced by injection of parental C57BL/6 splenocytes into unirradiated (C57BL/6 x DBA/2) F1 hybrids. FTS treatment significantly protected mice from developing acute GVHD as assessed by mortality rate, splenomegaly and enteropathy. The infiltration of donor-derived TCR alpha beta i-IEL bearing CD8 alpha beta was significantly inhibited in the small intestine of FTS-treated mice, and the frequencies of apoptosis of crypt cells in the intestinal mucosa were decreased in these mice during acute GVHD. These results suggest that FTS treatment contributes to protection against enteropathy of acute GVHD. Thus, FTS may provide a useful approach to control acute GVHD after blood transfusion or bone marrow transplantation.

Topics: Animals; Apoptosis; Female; Flow Cytometry; Graft vs Host Disease; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Lymphocytes; Mice; Mice, Inbred C57BL; Splenomegaly; Thymic Factor, Circulating; Tissue Donors

Thymulin (FTS-Zn) is a synthetic metallo-nonapeptide similar to the serum factor of thymic origin FTS, which induces the maturation of lymphoid cells. The activity of this compound on peripheral blood mononuclear cells from 12 bone marrow recipients was studied in vitro. It was demonstrated that thymulin was able to induce or modulate the expression of T-cell membrane markers, to enhance the proliferative responsiveness of lymphocytes to mitogens or allogeneic cells, and to increase mononuclear cells' natural killer activity. This in vitro responsiveness was contemporary to a transient decrease of FTS levels in the patients' serum, documented by sequential assays. These results suggest that thymulin could be of interest as a prophylactic therapy to speed up the immunological reconstitution of bone marrow recipients.

Topics: Adolescent; Antigens, Surface; Bone Marrow Transplantation; Child; Child, Preschool; Cytomegalovirus Infections; Female; Graft vs Host Disease; Humans; Infant; Interferon Type I; Killer Cells, Natural; Lymphocyte Activation; Male; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones