Mycophenolic acid (MPA), administered orally to mice, inhibits the formation of antibodies to sheep erythrocytes. MPA also suppresses, in a dose-related manner, the generation of cytotoxic T-lymphocytes against allogeneic cells in mice and prevents the elimination of allogeneic cells. However, short-term of T lymphocytes with therapeutically attainable doses of MPA does not inhibit the effector phase of cytotoxicity. Doses of MPA sufficient to prevent allograft rejection in mice inhibit the incorporation of labelled thymidine into DNA in the lymph nodes and spleen of mice but not in the germinal cells of the testis or in the basal epithelial cells of the jejunum; they do not produce neutropenia, anaemia or thrombocytopenia. These observations show that MPA has lymphocyte-selective anti-proliferative effects in vivo and can inhibit both cell-mediated and humoral immune responses without major side effects. Reasons why MPA has advantages over currently used and recently identified immunosuppressive drugs are discussed. The experimental system described provides a convenient in vivo assay for the capacity of drugs to inhibit allograft rejection.

Increased apoptosis and terminal differentiation of both lymphocytes and monocytes may promote the antiproliferative, immunosuppressive, and anti-inflammatory effects of MMF seen clinically in transplantation and rheumatoid arthritis.

When polymorphonuclear leukocytes (PMNs) and mononuclear cells were isolated from the blood of dexamethasone-treated normal rats, in vitro mononuclear cell migration was inhibited and PMN migration was stimulated in comparison to controls. Inflammogen-induced PMNs showed inhibited cell migration due to dexamethasone treatment. Gamma camera imaging was then used to detect cells in vivo after labeling with indium-111. When the dexamethasone-treated blood cells were injected into adjuvant arthritis diseased rats, mononuclear cells showed depressed migration into the inflamed paws, while PMNs showed stimulated migration into the inflamed paws in comparison to controls. When the recipient adjuvant arthritic animals were treated with dexamethasone, both normal mononuclear cell and normal PMN migration to the inflamed paws were inhibited.

No abstract

The phenomenon of lymphocytotoxicity was demonstrated in 29 patients with mycosis fungoides, using a newly described epithelial cell culture system and an isotope marker, 125Iododeoxyuridine (125IUdR). Lymphocytotoxicity was demonstrated in patients in the generalized plaque and the erythroderma phases of the disease (P is less than or equal to 0.05). No significant lymphocytotoxicity was demonstrable in patients who were in the limited plaque (early) phase of the disease. It is hypothesized that this demonstration of lymphocytotoxicity in patients may be a manifestation of a delayed hypersensitivity response to an as yet unidentified antigen in the epidermis.