Toxic effects of recombinant tumor necrosis factor in suckling mice. Comparisons with interferon alpha/beta

Abstract

Newborn Swiss and A2G mice were given daily subcutaneous injections for 1 week of highly purified recombinant mouse tumor necrosis factor (TNF) or mouse interferon alpha/beta. Both treatments resulted in inhibition of growth of suckling mice and severe fatty changes and necrosis in the liver. The simultaneous injection of polyclonal antibody to interferon alpha/beta abrogated the effects of interferon but did not block the effects induced by TNF. The kidneys of TNF-treated suckling mice could be distinguished from interferon-treated mice by the absence of glomerular basement membrane abnormalities and the presence of numerous rounded eosinophilic hyaline granules within the cytoplasm of the proximal tubules. Treatment of suckling mice with TNF and interferon alpha/beta induced similar changes in the spleen and thymus. Interferon treatment of suckling A2G mice resulted in the appearance of pulmonary cysts, which were not observed in TNF-treated mice. It is concluded that the pattern of lesions induced in suckling mice by mouse TNF is both similar and different from that induced by mouse interferon alpha/beta.