PGG-Glucan, a Leukocyte-Specific Immunostimulant, Does Not Potentiate GVHD or Allograft Rejection

Abstract

PGG-glucan is an immunomodulator which can enhance the host response to infection. Phase I/II clinical trials have documented the safety and potential efficacy of this compound to reduce postoperative infectious complications in high risk surgical patients. Organ transplant recipients may benefit from this drug due to their high rates of postoperative infectious complications. A rat cardiac rejection model (ACI → Lew) and a mouse skin graft model (C3H/HeJ → B6AF1/J) were used with four treatment arms (control, Cyclo- sporine A (CsA), antilymphocyte serum (ALS), and CsA + ALS with and without PGG-glucan). Small intestinal allografts (Lew → LBNF1) were performed in rats to evaluate GVHD. In the mouse GVHD model, donor splenocytes were given to irradiated recipients (C57BL/6 → B6AF1), with and without PGG-glucan treatment. There was no difference in survival between PGG-glucan treatment and placebo for the control, CsA, and CsA + ALS groups in rat cardiac recipients. Recipients receiving ALS and treated with PGG-glucan survived a median of 42.5 days versus 63.5 days for those ALS-treated animals not receiving PGG-glucan (P= 0.045). In the remaining groups there was no difference in survival between PGG-glucan-treated groups and the control groups. PGG-glucan did not shorten survival in three of four treatment groups in the rat cardiac rejection model. High dose ALS with PGG-glucan did result in a marginal decrease in survival in cardiac allograft recipients. If the one outlying animal with indefinite survival is excluded, the difference is not statistically significant (P= 0.098). These results show that even though PGG-glucan has immunostimulatory properties, it does not significantly potentiate rejection or GVHD in these animal models. This preliminary work may be important in determining whether PGG-glucan can be safely given to immunosuppressed organ transplant recipients to reduce postoperative infectious complications.