TNFα-mediated tissue damage in mouse footpads primed with mycobacterial preparations

https://doi.org/10.1016/0923-2494(92)80041-IGet rights and content

Summary

Tissue sites involved in certain types of inflammation become sensitive to the destructive effect of a subsequent injection of tumour necrosis factor alpha (TIMFα). To try to further delineate the cascade of effector and regulatory events controlling this activity, a new model is described and its main properties characterized. C57BL/GrFa mice received mycobacterial products subcutaneously in the footpads. Recombinant TNFga was injected 24 h later into the same sites. To assess the tissue-destructive effect of TNFga in these “primed” footpads, swelling and haemoglobin content of injected footpads were measured, 16 h and 20 h respectively after the injection of TNFga. When loaded with either Escherichia coli LPS (10 μg) or Mycobacterium vaccae soluble sonicate (17 μg), footpads were reactive to the subsequent injection of (1 μg) recombinant TNFga, as assessed by both swelling and haemoglobin content. When C57BL/GrFa mice received 109 autoclaved M. vaccae subcutaneously in the back 10 days before the footpad was “primed” with soluble M. vaccae sonicate, the destructive effect of TNFga was significantly enhanced, becoming 5–10-fold greater than that seen in sites “primed” with an optimal dose of LPS. This higher reactivity was abrogated by a single dose of anti-CD4 given just before the injection of TNFga. This local reactivity to TNFga of skin sites loaded with mycobacterial products is compared to the local LPS-dependent Shwartzman reaction, and the relevance of this assay as a model with which to delineate the mechanisms of tissue damage in tuberculosis is discussed.

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