Administration of human rTNF to both male and female mice with severe, but clinically inapparent, lymphocytic choriomeningitis caused death within 2 to 3 h. The development of fatal symptoms was accompanied by a two- to threefold reduction in the number of cells present in the cerebrospinal fluid, with this effect being more apparent in female mice. Giving the same dose of rTNF earlier in the course of the disease was not fatal and reduced the level of subsequent meningitis. In addition, prior exposure to rTNF protected against the acute development of lethal disease when a second dose of the cytokine was given later. The extent of this "tolerance" to rTNF was directly related to the degree of reduction of the inflammatory process resulting from the primary exposure to the cytokine.

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