IMMUNOLOGICAL PRIMING ATTENUATES THE IN-VIVO PATHOPHYSIOLOGICAL RESPONSE TO LIPOPOLYSACCHARIDE - COMPARISON OF CYTOKINE PRODUCTION, TISSUE-INJURY, AND LETHALITY IN COMPLETE FREUNDS ADJUVANT-PRIMED MICE AND IN UNPRIMED MICE

Previous reports have indicated that immunological priming of animals will result in increased cytokine production and enhanced susceptibili ty to the toxicity of cytokines. We primed mice with complete Freund's adjuvant and challenged 2 weeks later with 1 mg/mouse of lipopolysacc haride. Primed mice produced less tumor necrosis factor than naive mic e (35 +/- 8 vs 108 +/- 20 ng/ml) and also less interleukin-6 (182 +/- 37 vs 639 +/- 155 ng/ml). Leukopenia developed only in the naive mice. Although neutropenia and lymphocytosis developed in both groups, the alterations manifested themselves more quickly in printed mice. Primed mice had substantially greater pulmonary neutrophil sequestration det ermined both enzymatically and histologically but no lung damage. Howe ver, primed mice had significantly less small bowel damage than naive mice. Mortality was substantially reduced in Primed mice compared with unprimed mice. These results demonstrate that immunological priming i n vivo decreases cytokine production in response to lipopolysaccharide challenge, decreases organ injury, and reduces mortality.