Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alpha-Galactosyl IgG antibodies

Natural alpha -Galactosyl (Gal) antibodies play an important role in the re jection of pig xenografts by humans and Old World monkeys. In this study we investigate the efficacy of two different strategies to reduce the serum l evel of natural anti-Gal antibodies. On the one hand, removal of aerobic gr am-negative bacteria from the intestinal flora, because anti-Gal antibodies appear to be produced as a result of the continuous sensitization by these microorganisms. On the other hand, we studied the effect on these antibodi es of an immunosuppressive regimen of cyclophosphamide and steroids. Ten ba boons were treated for three months with norfloxacin (Nor Group; n=6) or cy clophosphamide and steroids (CyP Group; n=4). A further four baboons did no t receive any treatment (Control Group). Aerobic gram-negative bacteria bec ame negative in stools of the Nor Group after two weeks of treatment, and r emained undetectable until week 7. Thereafter, a gradual increase on the fe cal concentration of aerobic gram-negative bacteria was observed despite th e norfloxacin treatment. The mean anti-Gal IgG in the Nor Group gradually d eclined from week 4 to 9 to a mean of 62.7+/-18% of the baseline level, and during this period were significantly lower than in the CyP (P<0.02) and t he Control(P<0.05) groups. No differences were observed between the three g roups during the 16 weeks of follow-up in serum levels of anti-Gal IgM, hem olytic anti-pig antibodies, total IgG, IgM and IgA. In conclusion, removal of normal aerobic gram-negative bacteria from the intestinal flora is more effective than immunosuppression with CyP and steroids in reducing the leve l of natural anti-Gal antibodies, although there is no discernible effect o n IgM antibodies.