Immunological priming attenuates the in vivo pathophysiological response to lipopolysaccharide. Comparison of cytokine production, tissue injury, and lethality in complete Freund's adjuvant-primed mice and in unprimed mice.
Previous reports have indicated that immunological priming of animals will result in increased cytokine production and enhanced susceptibility to the toxicity of cytokines. We primed mice with complete Freund's adjuvant and challenged 2 weeks later with 1 mg/mouse of lipopolysaccharide. Primed mice produced less tumor necrosis factor than naive mice (35 +/- 8 vs 108 +/- 20 ng/ml) and also less interleukin-6 (182 +/- 37 vs 6.39 +/- 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 primed mice. Primed mice had substantially greater pulmonary neutrophil sequestration determined both enzymatically and histologically but no lung damage. However, 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 in vivo decreases cytokine production in response to lipopolysaccharide challenge, decreases organ injury, and reduces mortality.
DeForge
L E
LE
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Takeuchi
E
E
Nguyen
D T
DT
Remick
D G
DG
D000818:Animals; D001772:Blood Cell Count; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007970:Leukopenia / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000473:pathology / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D008954:Models, Biological; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant