STUDIES ON PULMONARY TISSUE AFTER ADMINISTRATION OF MUTEIN VI-HREC TNF-ALPHA INTO IMPLANTABLE EXPERIMENTAL MORRIS HEPATOMA

Experiments were carried out on Buffalo rats with implantable Morris h epatoma 5123 growing in the skeletal muscles of the limbs. Mutein VI ( a protein which differs from the native TNF-alpha molecule in its N-te rminal amino acid composition) was administered at a dose of 10 mu g p er rat once a day in a cycle of 8 days. Control animals were given sal ine (PBS). Ultrastructural changes within the pulmonary tissue were ev aluated with an electron transmission microscope (TEM), with special a ttention paid to endothelial cells and alveolar epithelial cells. Quan titative analysis of neoplastic metastases to the lungs was carried ou t. The animals given mutein VI compared to those injected with PBS dem onstrated a decrease in the number of metastases. TEM pictures showed accumulations of eosinophilic granulocytes and monocytes in the lumen of the blood vessels. Enhanced activity of endothelial cells was obser ved. In pulmonary alveoli conglomerates of fibrin, and fragments of da maged cells were found, with erythrocytes, granulocytes and macrophage s in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The mutein VI-hrec TNF-alp ha was found to block the neoplastic process, illustrated by a reducti on in the volume of lung parenchyma occupied by neoplastic metastases. Also, the ultrastructural changes observed in the pulmonary tissue in dicate the possibility of peripheral action of mutein VI after its adm inistration to rats carrying the Morris hepatoma.