Immunomodulatory effect of synthetic branched polypeptides I

The immunomodulatory potential of poly-(Lys-[Leu-poly-DL-Ala]) (LAK) (Lys:Ala:Leu = 1:3:0.7) as the first prototype of a series of new branched polypeptides was studied. Circular dichroism spectra indicated a highly ordered structure of LAK at physiological pH. The ability of the polypeptide to stimulate antibody response to immunization with sheep red blood cells (SRBC) when applied in aqueous medium was assessed in BDF1 inbred normal mice by the hemolytic plaque-forming cell and rosette-forming cell (RFC) assays. LAK, similarly to levamisole (LEV), a clinically applied immunomodulator, stimulated the host's humoral immune response in a wide dose interval (0.02-20 mg/kg; optimal dose, 1 mg/kg); however, the number of RFC was not influenced considerably. LAK was not toxic in doses of up to 25 mg/kg. The varied timing of LAK treatment (1 mg/kg i.p.) relative to SRBC immunization resulted in an oscillating potentiation of the immune response. The immunoadjuvant activity elicited by LAK--similarly to LEV--was sufficient to produce effective compensation of immunosuppression induced by the cytotoxic drugs vincristine and dianhydrogalactitol when combined treatments on multiple schedules were applied before SRBC immunization.