Background. The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN→LEW, and on lymphocyte activation and cytokine gene expression in vitro. Methods. Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-γ was examined by reverse transcriptase-polymerase chain reaction. Results. The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P < 0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7±1.0, P < 0.05; interalveolar hemorrhage, 0 vs. 3.0±0.9, P < 0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-γmRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. Conclusions. 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and γ-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.
ASJC Scopus subject areas