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Effects of hyaluronan on models of immediate and delayed hypersensitivity in the rat
A R Moore1, D W Gilroy, P R Colville-Nash
1Department of Experimental Pathology, St Bartholomew's & Royal London School of Medicine & Dentistry, UK.
Others have previously shown that superoxide dismutase conjugated with hyaluronan (HA) retains enzymic activity but is non-immunogenic. Whether HA could be widely used to prevent sensitisation to protein/polypeptide therapeutics is not known. In this study we investigated the effects of HA on bovine serum albumin (BSA) and methylated BSA pleural reactions in sensitised rats (active Arthus and delayed hypersensitivity reactions respectively) and on a reverse passive Arthus reaction in which rats received an intravenous injection of rabbit immunoglobulin and intrapleural challenge with goat anti rabbit immunoglobulin. HA suppressed the active Arthus and delayed hypersensitivity models when administered at the time of sensitisation but only the delayed hypersensitivity model at the time of intrapleural challenge. HA did not modulate the reverse passive Arthus reaction. The results show no evidence that simple mixing of HA with antigens masks antigenic determinants. However, HA appeared to have suppressive effects on both antibody and cell-mediated immune reactions. Therefore it may not be necessary to conjugate protein/polypeptide therapeutics to HA in order to prevent immune sensitisation.
Others have previously shown that superoxide dismutase conjugated with hyaluronan (HA) retains enzymic activity but is non-immunogenic. Whether HA could be widely used to prevent sensitisation to protein/polypeptide therapeutics is not known. In this study we investigated the effects of HA on bovine serum albumin (BSA) and methylated BSA pleural reactions in sensitised rats (active Arthus and delayed hypersensitivity reactions respectively) and on a reverse passive Arthus reaction in which rats received an intravenous injection of rabbit immunoglobulin and intrapleural challenge with goat anti rabbit immunoglobulin. HA suppressed the active Arthus and delayed hypersensitivity models when administered at the time of sensitisation but only the delayed hypersensitivity model at the time of intrapleural challenge. HA did not modulate the reverse passive Arthus reaction. The results show no evidence that simple mixing of HA with antigens masks antigenic determinants. However, HA appeared to have suppressive effects on both antibody and cell-mediated immune reactions. Therefore it may not be necessary to conjugate protein/polypeptide therapeutics to HA in order to prevent immune sensitisation.