Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue development

doi:10.1084/jem.176.5.1259

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Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue development

S de Kossodo, GE Grau, T Daneva, P Pointaire, L Fossati, C Ody, J Zapf, PF Piguet, RC Gaillard and P Vassalli
Department of Pathology, University of Geneva, Switzerland.

Tumor necrosis factor alpha (TNF-alpha), a major mediator of inflammation, also possesses a wide pleiotropism of actions, suggesting its involvement in physiological conditions. TNF-alpha mRNA is present in mouse embryonic tissues and also in fetal thymus and spleen. Repeated injections of a monospecific polyclonal rabbit anti-mouse TNF- alpha antibody in mice, starting either during pregnancy or at birth, led to a severe but transient growth retardation, already present at birth, reaching a 35% decrease in body weight at 3 wk, with complete recovery at 8 wk. The insulin growth factor I (IGF-I) blood levels were decreased to about 50%; growth hormone release and other endocrine functions were unaltered. A marked atrophy of the thymus, spleen, and lymph nodes was also observed, with lymphopenia and impaired development of T and B cell peripheral lymphoid structures. The pathways involving TNF-alpha in IGF-I release and early body growth are probably distinct from those by which TNF-alpha participates in early development of lymphoid tissues, where its low physiological release may contribute to enhance lymphoid cell expansion.
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