PubMed · 7749311
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M Okuhara, T Kino. 1994. Immunomodulators.. https://doi.org/10.1016/b978-0-7506-9003-4.50018-6
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Costimulatory molecules help determine T cell responses. CD80 (B7-1) and CD86 (B7-2), costimulatory proteins on antigen-presenting cells, bind to CD28 on T cells. When costimulation is coupled with a signal through the T cell receptor (TCR), T cell proliferation and cytokine secretion are induced. However, TCR signaling without CD80/CD86CD28 costimulation causes anergy. During multiple sclerosis (MS) exacerbations, circulating immune cells are activated, Th1 cytokine levels in the blood are elevated, and blood-derived immune cells destroy brain oligodendroglia. In the experimental autoimmune encephalomyelitis model of MS, CD80 on antigen-presenting cells induces Th1 cell responses; CD86 enhances generation of Th2 cells. Variation in CD80 and CD86 expression is likely to influence immune regulation in MS. We demonstrate that the number of circulating CD80(+) lymphocytes is increased significantly during MS exacerbations, but is normal in stable MS. These CD80(+) lymphocytes are predominantly B cells, based on two-color flow cytometry. The number of CD71(+) and HLA-DR+ lymphocytes and monocytes is also increased in active MS. Therapy with IFN beta-1b markedly reduces the number of circulating CD80(+) B cells and increases CD86(+) monocyte number. HLA-DR+, CD71(+), and CD25(+) mononuclear cell numbers are also reduced by therapy. The number of CD80(+) cells may be a useful surrogate marker during IFN-beta therapy, and reduction of CD80-mediated costimulation may be one therapeutic mechanism by which IFN-beta acts in MS.
BACKGROUND: Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. METHODS: C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. RESULTS: In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). CONCLUSIONS: The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.