Poly(vinylpyridine oxides) in pneumoconiosis research.

Poly(vinylpyridine oxides) in pneumo-coniosis research. Schlipkoter and Brockhaus of the Institut fur Lufthygiene Dusseldorf found that poly(2-vinylpyridine 1-oxide) can inhibit the fibrosis normally produced by quartz dust in the lungs or other tissues of animals. Later research in Germany and elsewhere has confirmed the earlier observations. The polymer is active when the quartz is administered by intratracheal, intraperitoneal or intravenous injection or by inhalation. It is effective if given in aqueous solution by intraperitoneal or subcutaneous injection or if it is inhaled as an aerosol. The polymer also counteracts the cytotoxic effects of finely divided quartz in cultures of alveolar or peritoneal macrophages and a rapid method for comparing the activity is based on this observation. Although some solutions of this and other polymers which show activity against quartz in cultures are less active against quartz in the whole animal, a polymer which proves inactive against quartz in cultures is invariably inactive in the whole animal. The degree of activity of this polymer depends on the molecular weight, low molecular weight being associated with low activity. Methyl groups substituted in the pyridine ring may reduce the activity or may have no effect, depending on the position of the group in the ring. The isotactic and syndiotactic forms of the polymer do not have identical effects. Poly(2-vinylpyridine 1-oxide) is not unique; poly(dimethylaminostyrene N-oxide) is almost equally effective. Several theories seek to explain the activity of this polymer against quartz but there is uncertainty, particularly because the mechanism by which silica damages cells and produces fibrosis is still in doubt. Damage to the membrane of the cell or its ultrastructures by silica has been suggested as a possible cause of cytotoxicity; it has been suggested that the polymer may shield these structures. Other suggestions are that the polymer coats the surface of the quartz or combines with silicic acid by forming hydrogen bonds. When finely divided quartz is introduced into the lung of an animal by inhalation or injection, fibrosis of the lung results. Similarly, if the quartz is injected into the peritoneal cavity, fibrous nodules are produced. Schlipkoter and Brockhaus (1960) demonstrated that if the quartz (50 mg) was injected as a suspension in a 1 % solution of poly(2-vinyl-pyridine) (I) or poly(4-vinylpyridine) (II) in dilute acid, minimal fibrosis followed. The reduction of fibrosis was demonstrated histologically and by chemical estimation of the collagen in the tissue. It seemed probable that …