In vitro and in vivo immunomodulatory effects of microdispersed oxidized cellulose.

The immune system can be manipulated specifically by vaccination or nonspecifically by immunomodulation. Many of biological response modifiers (BRM) have polysaccharidic structure similar to that of microdispersed oxidized cellulose (MDOC). We have investigated the immunomodulatory activity of different inorganic MDOC salts (H, Na, Ca, Mg, Zn, Al, Co, Ca/Na) and organic MDOC derivatives (urea, gelatine, arginine) both in vitro and in vivo. A dose-dependent stimulation by a number of MDOC derivatives was observed with spontaneous and mitogen-induced proliferation of human peripheral blood leukocytes (PBLs) and mouse splenocytes in vitro. In both primary cultures, the most intensive proliferation was induced by a Ca/Na salt at a concentration of 1 mg/ml. We have also demonstrated stimulatory effects of MDOC Ca/Na salt on the mouse mixed leukocyte reaction (MLR). The stimulatory activity of MDOC towards the immune system was further supported by the fact that in vitro the product stimulates the release of Th1 cytokine TNF-alpha, but not IFN-gamma, IL-4 or IL-6. In vivo MDOC application increases more than 50% the number of colony-forming units spleen (CFU-s), i.e., stimulates the stem cells in bone marrow, and increases relative percentage of monocytes and B lymphocytes in the mouse peripheral blood.